Autophagy and mitochondria in obesity and type 2 diabetes

Current Diabetes Reviews

Volumn 12, Issue , 2016, Pages

  Sarparanta, Jaakko ^a   García Macia, Marina ^a   Singh, Rajat ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Adipose tissue; Beta cells; Diabetes; Macroautophagy; Mitophagy; Muscle

Indexed keywords

ADIPOSE TISSUE; AUTOPHAGY; CELL FUNCTION; DIABETIC CARDIOMYOPATHY; DIABETIC NEPHROPATHY; DIABETIC RETINOPATHY; ENDOPLASMIC RETICULUM STRESS; HUMAN; MITOCHONDRION; MITOPHAGY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXIDATIVE STRESS; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; REVIEW; SKELETAL MUSCLE; ANIMAL; INSULIN RESISTANCE; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; SIGNAL TRANSDUCTION;

INSULIN;

ADIPOSE TISSUE; ADIPOSITY; ANIMALS; AUTOPHAGY; DIABETES MELLITUS, TYPE 2; HUMANS; INSULIN; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; MITOCHONDRIA; MUSCLE, SKELETAL; OBESITY; OXIDATIVE STRESS; SIGNAL TRANSDUCTION;

EID: 84981548122     PISSN: 15733998     EISSN: 18756417     Source Type: Journal    
DOI: 10.2174/1573399812666160217122530     Document Type: Review

References (252)

1. International Diabetes Federation. IDF Diabetes Atlas, 6th edn: International Diabetes Federation; 2013 [cited 2015]. 6th: Available from: http://www.idf.org/diabetesatlas
2. Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis SA. Insulin effects in muscle and adipose tissue. Diabetes Res Clin Pract. 2011;93 Suppl 1:S52-9
3. Muoio DM, Newgard CB. Mechanisms of disease:Molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9(3):193-205
4. Duncan JG. Mitochondrial dysfunction in diabetic cardiomyopathy. Biochim Biophys Acta. 2011;1813(7):1351-9
5. Tewari S, Santos JM, Kowluru RA. Damaged mitochondrial DNA replication system and the development of diabetic retinopathy. Antioxid Redox Signal. 2012;17(3):492-504
6. Higgins GC, Coughlan MT. Mitochondrial dysfunction and mitophagy: the beginning and end to diabetic nephropathy? Br J Pharmacol. 2014;171(8):1917-42
7. Montgomery MK, Turner N. Mitochondrial dysfunction and insulin resistance: an update. Endocr Connect. 2015;4(1):R1-R15
8. Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012;13(9):566-78
9. Chandel NS. Mitochondria as signaling organelles. BMC Biol. 2014;12:34
10. Frey TG, Mannella CA. The internal structure of mitochondria. Trends Biochem Sci. 2000;25(7):319-24
11. Archer SL. Mitochondrial dynamics mitochondrial fission and fusion in human diseases. N Engl J Med. 2013;369(23):2236-51
12. Twig G, Elorza A, Molina AJ, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27(2):433-46
13. Scheibye-Knudsen M, Fang EF, Croteau DL, Wilson DM, 3rd, Bohr VA. Protecting the mitochondrial powerhouse. Trends Cell Biol. 2014
14. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20(3):460-73
15. Ravikumar B, Sarkar S, Davies JE, et al. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev. 2010;90(4):1383-435
16. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol. 2010;22(2):132-9
17. Efeyan A, Zoncu R, Sabatini DM. Amino acids and mTORC1: from lysosomes to disease. Trends Mol Med. 2012;18(9):524-33
18. Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331(6016):456-61
19. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132-41
20. Russell RC, Tian Y, Yuan H, et al. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol. 2013;15(7):741-50
21. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008;30(6):678-88
22. Shpilka T, Weidberg H, Pietrokovski S, Elazar Z. Atg8: an autophagy-related ubiquitin-like protein family. Genome Biol. 2011;12(7):226
23. Bai H, Inoue J, Kawano T, Inazawa J. A transcriptional variant of the LC3A gene is involved in autophagy and frequently inactivated in human cancers. Oncogene. 2012;31(40):4397-408
24. Maruyama Y, Sou YS, Kageyama S, et al. LC3B is indispensable for selective autophagy of p62 but not basal autophagy. Biochem Biophys Res Commun. 2014;446(1):309-15
25. Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19(21):5720-8
26. Komatsu M, Waguri S, Ueno T, et al. Impairment of starvationinduced and constitutive autophagy in Atg7-deficient mice. J Cell Biol. 2005;169(3):425-34
27. Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004;117(Pt 13):2805-12
28. Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell. 2008;19(5):2092-100
29. Klionsky DJ, Abdalla FC, Abeliovich H, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8(4):445-544
30. Rogov V, Dötsch V, Johansen T, Kirkin V. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell. 2014;53(2):167-78
31. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183(5):795-803
32. Matsuda N, Sato S, Shiba K, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189(2):211-21
33. Okatsu K, Uno M, Koyano F, et al. A dimeric PINK1-containing complex on depolarized mitochondria stimulates Parkin recruitment. J Biol Chem. 2013;288(51):36372-84
34. Drew BG, Ribas V, Le JA, et al. HSP72 is a mitochondrial stress sensor critical for Parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle. Diabetes. 2014;63(5):1488-505
35. Iguchi M, Kujuro Y, Okatsu K, et al. Parkin-catalyzed ubiquitinester transfer is triggered by PINK1-dependent phosphorylation. J Biol Chem. 2013;288(30):22019-32
36. Koyano F, Okatsu K, Kosako H, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014;510(7503):162-6
37. Okatsu K, Oka T, Iguchi M, et al. PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun. 2012;3:1016
38. Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet. 2010;19(24):4861-70
39. Geisler S, Holmström KM, Skujat D, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12(2):119-31
40. Tanaka A, Cleland MM, Xu S, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol. 2010;191(7):1367-80
41. Chan NC, Salazar AM, Pham AH, et al. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet. 2011;20(9):1726-37
42. Rakovic A, Shurkewitsch K, Seibler P, et al. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J Biol Chem. 2013;288(4):2223-37
43. Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy. 2010;6(8):1090-106
44. Wong YC, Holzbaur EL. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A. 2014;111(42):E4439-48
45. Scarffe LA, Stevens DA, Dawson VL, Dawson TM. Parkin and PINK1: much more than mitophagy. Trends Neurosci. 2014;37(6):315-24
46. Novak I, Kirkin V, McEwan DG, et al. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010;11(1):45-51
47. Fu M, St-Pierre P, Shankar J, Wang PT, Joshi B, Nabi IR. Regulation of mitophagy by the Gp78 E3 ubiquitin ligase. Mol Biol Cell. 2013;24(8):1153-62
48. Liu L, Feng D, Chen G, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012;14(2):177-85
49. Chu CT, Ji J, Dagda RK, et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol. 2013;15(10):1197-205
50. Strappazzon F, Nazio F, Corrado M, et al. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ. 2014
51. Van Humbeeck C, Cornelissen T, Hofkens H, et al. Parkin interacts with Ambra1 to induce mitophagy. J Neurosci. 2011;31(28):10249-61
52. Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism. Nature. 2009;458(7242):1131-5
53. Kaushik S, Rodriguez-Navarro JA, Arias E, et al. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab. 2011;14(2):173-83
54. Kaushik S, Arias E, Kwon H, et al. Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO Rep. 2012;13(3):258-65
55. Baron AD, Brechtel G, Wallace P, Edelman SV. Rates and tissue sites of non-insulinand insulin-mediated glucose uptake in humans. Am J Physiol. 1988;255(6 Pt 1):E769-74
56. Goodpaster BH. Mitochondrial deficiency is associated with insulin resistance. Diabetes. 2013;62(4):1032-5
57. Holloszy JO. “Deficiency” of mitochondria in muscle does not cause insulin resistance. Diabetes. 2013;62(4):1036-40
58. Kelley DE, Goodpaster B, Wing RR, Simoneau JA. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol. 1999;277(6 Pt 1):E1130-41
59. Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes. 2002;51(10):2944-50
60. Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes. 2005;54(1):8-14
61. Kim JY, Hickner RC, Cortright RL, Dohm GL, Houmard JA. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab. 2000;279(5):E1039-44
62. Morino K, Petersen KF, Dufour S, et al. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest. 2005;115(12):3587-93
63. Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsøe R, Dela F. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia. 2007;50(4):790-6
64. Heilbronn LK, Gan SK, Turner N, Campbell LV, Chisholm DJ. Markers of mitochondrial biogenesis and metabolism are lower in overweight and obese insulin-resistant subjects. J Clin Endocrinol Metab. 2007;92(4):1467-73
65. Ukropcova B, Sereda O, de Jonge L, et al. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle. Diabetes. 2007;56(3):720-7
66. Chomentowski P, Coen PM, Radiková Z, Goodpaster BH, Toledo FG. Skeletal muscle mitochondria in insulin resistance: differences in intermyofibrillar versus subsarcolemmal subpopulations and relationship to metabolic flexibility. J Clin Endocrinol Metab. 2011;96(2):494-503
67. Coen PM, Hames KC, Leachman EM, et al. Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity. Obesity (Silver Spring). 2013;21(11):2362-71
68. Mootha VK, Lindgren CM, Eriksson KF, et al. PGC-1alpharesponsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267-73
69. Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A. 2003;100(14):8466-71
70. Hwang H, Bowen BP, Lefort N, et al. Proteomics analysis of human skeletal muscle reveals novel abnormalities in obesity and type 2 diabetes. Diabetes. 2010;59(1):33-42
71. Mogensen M, Sahlin K, Fernström M, et al. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes. 2007;56(6):1592-9
72. Phielix E, Schrauwen-Hinderling VB, Mensink M, et al. Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients. Diabetes. 2008;57(11):2943-9
73. Rabøl R, Larsen S, Højberg PM, et al. Regional anatomic differences in skeletal muscle mitochondrial respiration in type 2 diabetes and obesity. J Clin Endocrinol Metab. 2010;95(2):857-63
74. Larsen S, Stride N, Hey-Mogensen M, et al. Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes. Diabetologia. 2011;54(6):1427-36
75. Asmann YW, Stump CS, Short KR, et al. Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia. Diabetes. 2006;55(12):3309-19
76. Larsen S, Skaaby S, Helge JW, Dela F. Effects of exercise training on mitochondrial function in patients with type 2 diabetes. World J Diabetes. 2014;5(4):482-92
77. Wredenberg A, Freyer C, Sandström ME, et al. Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance. Biochem Biophys Res Commun. 2006;350(1):202-7
78. Bonnard C, Durand A, Peyrol S, et al. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J Clin Invest. 2008;118(2):789-800
79. Fisher-Wellman KH, Weber TM, Cathey BL, et al. Mitochondrial respiratory capacity and content are normal in young insulinresistant obese humans. Diabetes. 2014;63(1):132-41
80. Koves TR, Ussher JR, Noland RC, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 2008;7(1):45-56
81. Noland RC, Koves TR, Seiler SE, et al. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J Biol Chem. 2009;284(34):22840-52
82. Schooneman MG, Vaz FM, Houten SM, Soeters MR. Acylcarnitines: reflecting or inflicting insulin resistance? Diabetes. 2013;62(1):1-8
83. Aguer C, McCoin CS, Knotts TA, et al. Acylcarnitines: potential implications for skeletal muscle insulin resistance. FASEB J. 2015;29(1):336-45
84. Amati F, Dube JJ, Alvarez-Carnero E, et al. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes. 2011;60(10):2588-97
85. Henstridge DC, Bruce CR, Drew BG, et al. Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance. Diabetes. 2014;63(6):1881-94
86. Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med. 2011;50(5):567-75
87. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335-44
88. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40(4):405-12
89. Taylor ER, Hurrell F, Shannon RJ, Lin TK, Hirst J, Murphy MP. Reversible glutathionylation of complex I increases mitochondrial superoxide formation. J Biol Chem. 2003;278(22):19603-10
90. Indo HP, Davidson M, Yen HC, et al. Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage. Mitochondrion. 2007;7(1-2):106-18
91. Giardino I, Edelstein D, Brownlee M. BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells. J Clin Invest. 1996;97(6):1422-8
92. Gudz TI, Tserng KY, Hoppel CL. Direct inhibition of mitochondrial respiratory chain complex III by cell-permeable ceramide. J Biol Chem. 1997;272(39):24154-8
93. Cocco T, Di Paola M, Papa S, Lorusso M. Arachidonic acid interaction with the mitochondrial electron transport chain promotes reactive oxygen species generation. Free Radic Biol Med. 1999;27(1-2):51-9
94. Loskovich MV, Grivennikova VG, Cecchini G, Vinogradov AD. Inhibitory effect of palmitate on the mitochondrial NADH:ubiquinone oxidoreductase (complex I) as related to the active-de-active enzyme transition. Biochem J. 2005;387(Pt 3):677-83
95. Schönfeld P, Wojtczak L. Fatty acids decrease mitochondrial generation of reactive oxygen species at the reverse electron transport but increase it at the forward transport. Biochim Biophys Acta. 2007;1767(8):1032-40
96. Abdul-Ghani MA, Muller FL, Liu Y, et al. Deleterious action of FA metabolites on ATP synthesis: possible link between lipotoxicity, mitochondrial dysfunction, and insulin resistance. Am J Physiol Endocrinol Metab. 2008;295(3):E678-85
97. Sauer SW, Okun JG, Hoffmann GF, Koelker S, Morath MA. Impact of shortand medium-chain organic acids, acylcarnitines, and acyl-CoAs on mitochondrial energy metabolism. Biochim Biophys Acta. 2008;1777(10):1276-82
98. Lambertucci RH, Hirabara SM, Silveira Ldos R, Levada-Pires AC, Curi R, Pithon-Curi TC. Palmitate increases superoxide production through mitochondrial electron transport chain and NADPH oxidase activity in skeletal muscle cells. J Cell Physiol. 2008;216(3):796-804
99. Seifert EL, Estey C, Xuan JY, Harper ME. Electron transport chain-dependent and -independent mechanisms of mitochondrial H2O2 emission during long-chain fatty acid oxidation. J Biol Chem. 2010;285(8):5748-58
100. Montgomery MK, Osborne B, Brown SH, et al. Contrasting metabolic effects of mediumversus long-chain fatty acids in skeletal muscle. J Lipid Res. 2013;54(12):3322-33
101. Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006;440(7086):944-8
102. Hoehn KL, Salmon AB, Hohnen-Behrens C, et al. Insulin resistance is a cellular antioxidant defense mechanism. Proc Natl Acad Sci U S A. 2009;106(42):17787-92
103. Anderson EJ, Lustig ME, Boyle KE, et al. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest. 2009;119(3):573-81
104. Lefort N, Glancy B, Bowen B, et al. Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle. Diabetes. 2010;59(10):2444-52
105. Yokota T, Kinugawa S, Hirabayashi K, et al. Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2009;297(3):H1069-77
106. Lee HY, Choi CS, Birkenfeld AL, et al. Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. Cell Metab. 2010;12(6):668-74
107. Bravard A, Bonnard C, Durand A, et al. Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice. Am J Physiol Endocrinol Metab. 2011;300(3):E581-91
108. Perreault M, Marette A. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med. 2001;7(10):1138-43
109. Mahadev K, Motoshima H, Wu X, et al. The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. Mol Cell Biol. 2004;24(5):1844-54
110. Carvalho-Filho MA, Ueno M, Hirabara SM, et al. S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt: a novel mechanism of insulin resistance. Diabetes. 2005;54(4):959-67
111. Sugita H, Fujimoto M, Yasukawa T, et al. Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem. 2005;280(14):14203-11
112. Zhang Y, Qi H, Taylor R, Xu W, Liu LF, Jin S. The role of autophagy in mitochondria maintenance: characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains. Autophagy. 2007;3(4):337-46
113. Dagda RK, Cherra SJ, 3rd, Kulich SM, Tandon A, Park D, Chu CT. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem. 2009;284(20):13843-55
114. Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci U S A. 2009;106(8):2770-5
115. Wu JJ, Quijano C, Chen E, et al. Mitochondrial dysfunction and oxidative stress mediate the physiological impairment induced by the disruption of autophagy. Aging (Albany NY). 2009;1(4):425-37
116. Kurihara Y, Kanki T, Aoki Y, et al. Mitophagy plays an essential role in reducing mitochondrial production of reactive oxygen species and mutation of mitochondrial DNA by maintaining mitochondrial quantity and quality in yeast. J Biol Chem. 2012;287(5):3265-72
117. Scherz-Shouval R, Elazar Z. Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci. 2011;36(1):30-8
118. Filomeni G, De Zio D, Cecconi F. Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ. 2014
119. Auciello FR, Ross FA, Ikematsu N, Hardie DG. Oxidative stress activates AMPK in cultured cells primarily by increasing cellular AMP and/or ADP. FEBS Lett. 2014;588(18):3361-6
120. Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 2007;26(7):1749-60
121. Frank M, Duvezin-Caubet S, Koob S, et al. Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner. Biochim Biophys Acta. 2012;1823(12):2297-310
122. Wang Y, Nartiss Y, Steipe B, McQuibban GA, Kim PK. ROS-induced mitochondrial depolarization initiates PARK2/PARKIN-dependent mitochondrial degradation by autophagy. Autophagy. 2012;8(10):1462-76
123. Masiero E, Agatea L, Mammucari C, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009;10(6):507-15
124. Chung J, Nguyen AK, Henstridge DC, et al. HSP72 protects against obesity-induced insulin resistance. Proc Natl Acad Sci U S A. 2008;105(5):1739-44
125. Kim KY, Stevens MV, Akter MH, et al. Parkin is a lipidresponsive regulator of fat uptake in mice and mutant human cells. J Clin Invest. 2011;121(9):3701-12
126. He C, Bassik MC, Moresi V, et al. Exercise-induced BCL2regulated autophagy is required for muscle glucose homeostasis. Nature. 2012;481(7382):511-5
127. Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW. 5’ AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes. 1999;48(8):1667-71
128. Klueber KM, Feczko JD, Schmidt G, Watkins JB, 3rd. Skeletal muscle in the diabetic mouse: histochemical and morphometric analysis. Anat Rec. 1989;225(1):41-5
129. Krause MP, Riddell MC, Hawke TJ. Effects of type 1 diabetes mellitus on skeletal muscle: clinical observations and physiological mechanisms. Pediatr Diabetes. 2011;12(4 Pt 1):345-64
130. Park SW, Goodpaster BH, Strotmeyer ES, et al. Decreased muscle strength and quality in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes. 2006;55(6):1813-8
131. Park SW, Goodpaster BH, Strotmeyer ES, et al. Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes Care. 2007;30(6):1507-12
132. D’Souza DM, Al-Sajee D, Hawke TJ. Diabetic myopathy: impact of diabetes mellitus on skeletal muscle progenitor cells. Front Physiol. 2013;4:379
133. Price SR, Bailey JL, Wang X, et al. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest. 1996;98(8):1703-8
134. Sala D, Ivanova S, Plana N, et al. Autophagy-regulating TP53INP2 mediates muscle wasting and is repressed in diabetes. J Clin Invest. 2014;124(5):1914-27
135. Finegold JA, Asaria P, Francis DP. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol. 2013;168(2):934-45
136. Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5):1930-5
137. Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell. 2001;104(4):531-43
138. Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509-17
139. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293(2):E444-52
140. Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360(15):1518-25
141. Tiraby C, Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol Metab. 2003;14(10):439-41
142. Singh R, Xiang Y, Wang Y, et al. Autophagy regulates adipose mass and differentiation in mice. J Clin Invest. 2009;119(11):3329-39
143. Wu J, Bostrom P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366-76
144. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem. 2010;285(10):7153-64
145. Zhang Y, Goldman S, Baerga R, Zhao Y, Komatsu M, Jin S. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci U S A. 2009;106(47):19860-5
146. Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell. 2007;131(2):242-56
147. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab. 2006;4(4):263-73
148. Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol. 2000;16:145-71
149. Wilson-Fritch L, Burkart A, Bell G, et al. Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol. 2003;23(3):1085-94
150. Goldman S, Zhang Y, Jin S. Autophagy and adipogenesis: implications in obesity and type II diabetes. Autophagy. 2010;6(1):179-81
151. Franckhauser S, Munoz S, Pujol A, et al. Increased fatty acid reesterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance. Diabetes. 2002;51(3):624-30
152. Goldman SJ, Zhang Y, Jin S. Autophagic degradation of mitochondria in white adipose tissue differentiation. Antioxid Redox Signal. 2011;14(10):1971-8
153. Baerga R, Zhang Y, Chen PH, Goldman S, Jin S. Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice. Autophagy. 2009;5(8):1118-30
154. Skop V, Cahova M, Dankova H, et al. Autophagy inhibition in early but not in later stages prevents 3T3-L1 differentiation: Effect on mitochondrial remodeling. Differentiation. 2014;87(5):220-9
155. Ro SH, Jung CH, Hahn WS, et al. Distinct functions of Ulk1 and Ulk2 in the regulation of lipid metabolism in adipocytes. Autophagy. 2013;9(12):2103-14
156. Polak P, Cybulski N, Feige JN, Auwerx J, Ruegg MA, Hall MN. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab. 2008;8(5):399-410
157. Bell A, Grunder L, Sorisky A. Rapamycin inhibits human adipocyte differentiation in primary culture. Obes Res. 2000;8(3):249-54
158. Yeh WC, Bierer BE, McKnight SL. Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells. Proc Natl Acad Sci U S A. 1995;92(24):11086-90
159. Ost A, Svensson K, Ruishalme I, et al. Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes. Mol Med. 2010;16(7-8):235-46
160. Kovsan J, Bluher M, Tarnovscki T, et al. Altered autophagy in human adipose tissues in obesity. J Clin Endocrinol Metab. 2011;96(2):E268-77
161. Wasko MC, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA. 2007;298(2):187-93
162. Ahren B. Type 2 diabetes, insulin secretion and beta-cell mass. Curr Mol Med. 2005;5(3):275-86
163. Masini M, Bugliani M, Lupi R, et al. Autophagy in human type 2 diabetes pancreatic beta cells. Diabetologia. 2009;52(6):1083-6
164. Fujimoto K, Hanson PT, Tran H, et al. Autophagy regulates pancreatic beta cell death in response to Pdx1 deficiency and nutrient deprivation. J Biol Chem. 2009;284(40):27664-73
165. Ebato C, Uchida T, Arakawa M, et al. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab. 2008;8(4):325-32
166. Jung HS, Chung KW, Won Kim J, et al. Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab. 2008;8(4):318-24
167. Quan W, Hur KY, Lim Y, et al. Autophagy deficiency in beta cells leads to compromised unfolded protein response and progression from obesity to diabetes in mice. Diabetologia. 2012;55(2):392-403
168. Bartolomé A, Kimura-Koyanagi M, Asahara S, et al. Pancreatic beta-cell failure mediated by mTORC1 hyperactivity and autophagic impairment. Diabetes. 2014;63(9):2996-3008
169. Um SH, Frigerio F, Watanabe M, et al. Absence of S6K1 protects against ageand diet-induced obesity while enhancing insulin sensitivity. Nature. 2004;431(7005):200-5
170. Shigeyama Y, Kobayashi T, Kido Y, et al. Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice. Mol Cell Biol. 2008;28(9):2971-9
171. Choi SE, Lee SM, Lee YJ, et al. Protective role of autophagy in palmitate-induced INS-1 beta-cell death. Endocrinology. 2009;150(1):126-34
172. Komiya K, Uchida T, Ueno T, et al. Free fatty acids stimulate autophagy in pancreatic beta-cells via JNK pathway. Biochem Biophys Res Commun. 2010;401(4):561-7
173. Martino L, Masini M, Novelli M, et al. Palmitate activates autophagy in INS-1E beta-cells and in isolated rat and human pancreatic islets. PLoS One. 2012;7(5):e36188
174. Las G, Serada SB, Wikstrom JD, Twig G, Shirihai OS. Fatty acids suppress autophagic turnover in beta-cells. J Biol Chem. 2011;286(49):42534-44
175. Maechler P, Li N, Casimir M, Vetterli L, Frigerio F, Brun T. Role of mitochondria in beta-cell function and dysfunction. Adv Exp Med Biol. 2010;654:193-216
176. Lu H, Koshkin V, Allister EM, Gyulkhandanyan AV, Wheeler MB. Molecular and metabolic evidence for mitochondrial defects associated with beta-cell dysfunction in a mouse model of type 2 diabetes. Diabetes. 2010;59(2):448-59
177. Soleimanpour SA, Gupta A, Bakay M, et al. The diabetes susceptibility gene Clec16a regulates mitophagy. Cell. 2014;157(7):1577-90
178. Tanaka Y, Tran PO, Harmon J, Robertson RP. A role for glutathione peroxidase in protecting pancreatic beta cells against oxidative stress in a model of glucose toxicity. Proc Natl Acad Sci U S A. 2002;99(19):12363-8
179. Oprescu AI, Bikopoulos G, Naassan A, et al. Free fatty acidinduced reduction in glucose-stimulated insulin secretion: evidence for a role of oxidative stress in vitro and in vivo. Diabetes. 2007;56(12):2927-37
180. Li N, Brun T, Cnop M, Cunha DA, Eizirik DL, Maechler P. Transient oxidative stress damages mitochondrial machinery inducing persistent beta-cell dysfunction. J Biol Chem. 2009;284(35):23602-12
181. Krauss S, Zhang CY, Scorrano L, et al. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest. 2003;112(12):1831-42
182. Joseph JW, Koshkin V, Saleh MC, et al. Free fatty acid-induced beta-cell defects are dependent on uncoupling protein 2 expression. J Biol Chem. 2004;279(49):51049-56
183. Harmon JS, Stein R, Robertson RP. Oxidative stress-mediated, post-translational loss of MafA protein as a contributing mechanism to loss of insulin gene expression in glucotoxic beta cells. J Biol Chem. 2005;280(12):11107-13
184. Hoshino A, Ariyoshi M, Okawa Y, et al. Inhibition of p53 preserves Parkin-mediated mitophagy and pancreatic beta-cell function in diabetes. Proc Natl Acad Sci U S A. 2014;111(8):3116-21
185. Biden TJ, Boslem E, Chu KY, Sue N. Lipotoxic endoplasmic reticulum stress, beta cell failure, and type 2 diabetes mellitus. Trends Endocrinol Metab. 2014;25(8):389-98
186. Costes S, Huang CJ, Gurlo T, et al. beta-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency. Diabetes. 2011;60(1):227-38
187. Yorimitsu T, Nair U, Yang Z, Klionsky DJ. Endoplasmic reticulum stress triggers autophagy. J Biol Chem. 2006;281(40):30299-304
188. Ogata M, Hino S, Saito A, et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006;26(24):9220-31
189. Kouroku Y, Fujita E, Tanida I, et al. ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 2007;14(2):230-9
190. Fujita E, Kouroku Y, Isoai A, et al. Two endoplasmic reticulumassociated degradation (ERAD) systems for the novel variant of the mutant dysferlin: ubiquitin/proteasome ERAD(I) and autophagy/lysosome ERAD(II). Hum Mol Genet. 2007;16(6):618-29
191. Kamimoto T, Shoji S, Hidvegi T, et al. Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity. J Biol Chem. 2006;281(7):4467-76
192. Ishida Y, Yamamoto A, Kitamura A, et al. Autophagic elimination of misfolded procollagen aggregates in the endoplasmic reticulum as a means of cell protection. Mol Biol Cell. 2009;20(11):2744-54
193. Houck SA, Ren HY, Madden VJ, et al. Quality control autophagy degrades soluble ERAD-resistant conformers of the misfolded membrane protein GnRHR. Mol Cell. 2014;54(1):166-79
194. Schuit FC, In’t Veld PA, Pipeleers DG. Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells. Proc Natl Acad Sci U S A. 1988;85(11):3865-9
195. Yamamoto E, Uchida T, Abe H, et al. Increased expression of ERp57/GRP58 is protective against pancreatic beta cell death caused by autophagic failure. Biochem Biophys Res Commun. 2014;453(1):19-24
196. Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306(5695):457-61
197. Laybutt DR, Preston AM, Akerfeldt MC, et al. Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia. 2007;50(4):752-63
198. Huang CJ, Lin CY, Haataja L, et al. High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress mediated beta-cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes. Diabetes. 2007;56(8):2016-27
199. Marchetti P, Bugliani M, Lupi R, et al. The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia. 2007;50(12):2486-94
200. Cunha DA, Hekerman P, Ladrière L, et al. Initiation and execution of lipotoxic ER stress in pancreatic beta-cells. J Cell Sci. 2008;121(Pt 14):2308-18
201. Boslem E, MacIntosh G, Preston AM, et al. A lipidomic screen of palmitate-treated MIN6 beta-cells links sphingolipid metabolites with endoplasmic reticulum (ER) stress and impaired protein trafficking. Biochem J. 2011;435(1):267-76
202. Boslem E, Weir JM, MacIntosh G, et al. Alteration of endoplasmic reticulum lipid rafts contributes to lipotoxicity in pancreatic betacells. J Biol Chem. 2013;288(37):26569-82
203. Preston AM, Gurisik E, Bartley C, Laybutt DR, Biden TJ. Reduced endoplasmic reticulum (ER)-to-Golgi protein trafficking contributes to ER stress in lipotoxic mouse beta cells by promoting protein overload. Diabetologia. 2009;52(11):2369-73
204. Cardozo AK, Ortis F, Storling J, et al. Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells. Diabetes. 2005;54(2):452-61
205. Lee JW, Kim WH, Yeo J, Jung MH. ER stress is implicated in mitochondrial dysfunction-induced apoptosis of pancreatic beta cells. Mol Cells. 2010;30(6):545-9
206. Haataja L, Gurlo T, Huang CJ, Butler PC. Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis. Endocr Rev. 2008;29(3):303-16
207. Westermark P, Wernstedt C, O’Brien TD, Hayden DW, Johnson KH. Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone. Am J Pathol. 1987;127(3):414-7
208. Gurlo T, Ryazantsev S, Huang CJ, et al. Evidence for proteotoxicity in beta cells in type 2 diabetes: toxic islet amyloid polypeptide oligomers form intracellularly in the secretory pathway. Am J Pathol. 2010;176(2):861-9
209. Kim J, Cheon H, Jeong YT, et al. Amyloidogenic peptide oligomer accumulation in autophagy-deficient beta cells induces diabetes. J Clin Invest. 2014;124(8):3311-24
210. Rivera JF, Costes S, Gurlo T, Glabe CG, Butler PC. Autophagy defends pancreatic beta cells from human islet amyloid polypeptide-induced toxicity. J Clin Invest. 2014;124(8):3489-500
211. Shigihara N, Fukunaka A, Hara A, et al. Human IAPP-induced pancreatic beta cell toxicity and its regulation by autophagy. J Clin Invest. 2014;124(8):3634-44
212. Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC. The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes. 1999;48(3):491-8
213. Marsh BJ, Soden C, Alarcón C, et al. Regulated autophagy controls hormone content in secretory-deficient pancreatic endocrine betacells. Mol Endocrinol. 2007;21(9):2255-69
214. Bartolomé A, Guillén C, Benito M. Autophagy plays a protective role in endoplasmic reticulum stress-mediated pancreatic beta cell death. Autophagy. 2012;8(12):1757-68
215. Bachar-Wikstrom E, Wikstrom JD, Ariav Y, et al. Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes. Diabetes. 2013;62(4):1227-37
216. Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Signal. 2010;12(4):537-77
217. Kassab A, Piwowar A. Cell oxidant stress delivery and cell dysfunction onset in type 2 diabetes. Biochimie. 2012;94(9):1837-48
218. Gonzalez CD, Lee MS, Marchetti P, et al. The emerging role of autophagy in the pathophysiology of diabetes mellitus. Autophagy. 2011;7(1):2-11
219. Liu HY, Han J, Cao SY, et al. Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes by insulin. J Biol Chem. 2009;284(45):31484-92
220. Park KJ, Lee SH, Kim TI, et al. A human scFv antibody against TRAIL receptor 2 induces autophagic cell death in both TRAILsensitive and TRAIL-resistant cancer cells. Cancer Res. 2007;67(15):7327-34
221. Gilbertson DT, Liu J, Xue JL, et al. Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol. 2005;16(12):3736-41
222. de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2011;305(24):2532-9
223. Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 2011;378(9785):31-40
224. Gonzalez Suarez ML, Thomas DB, Barisoni L, Fornoni A. Diabetic nephropathy: Is it time yet for routine kidney biopsy? World J Diabetes. 2013;4(6):245-55
225. Soltoff SP. ATP and the regulation of renal cell function. Annu Rev Physiol. 1986;48:9-31
226. Tan AL, Sourris KC, Harcourt BE, et al. Disparate effects on renal and oxidative parameters following RAGE deletion, AGE accumulation inhibition, or dietary AGE control in experimental diabetic nephropathy. Am J Physiol Renal Physiol. 2010;298(3):F763-70
227. Huber TB, Edelstein CL, Hartleben B, et al. Emerging role of autophagy in kidney function, diseases and aging. Autophagy. 2012;8(7):1009-31
228. Takahashi A, Kimura T, Takabatake Y, et al. Autophagy guards against cisplatin-induced acute kidney injury. Am J Pathol. 2012;180(2):517-25
229. Kimura T, Takabatake Y, Takahashi A, et al. Autophagy protects the proximal tubule from degeneration and acute ischemic injury. J Am Soc Nephrol. 2011;22(5):902-13
230. Chiang YY, Wang SL, Yang CL, et al. Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects. Int J Mol Med. 2013;32(3):577-84
231. Ferree A, Guillily M, Li H, et al. Regulation of physiologic actions of LRRK2: focus on autophagy. Neurodegener Dis. 2012;10(1-4):238-41
232. Gray S, Kim JK. New insights into insulin resistance in the diabetic heart. Trends Endocrinol Metab. 2011;22(10):394-403
233. Palomer X, Salvado L, Barroso E, Vazquez-Carrera M. An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. Int J Cardiol. 2013;168(4):3160-72
234. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation. 2007;115(25):3213-23
235. Montaigne D, Marechal X, Coisne A, et al. Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients. Circulation. 2014;130(7):554-64
236. Magnusdottir S, Fillmore P, den Ouden DB, et al. Damage to left anterior temporal cortex predicts impairment of complex syntactic processing: a lesion-symptom mapping study. Hum Brain Mapp. 2013;34(10):2715-23
237. Jose C, Melser S, Benard G, Rossignol R. Mitoplasticity: adaptation biology of the mitochondrion to the cellular redox state in physiology and carcinogenesis. Antioxid Redox Signal. 2013;18(7):808-49
238. Yu T, Sheu SS, Robotham JL, Yoon Y. Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res. 2008;79(2):341-51
239. Shenouda SM, Widlansky ME, Chen K, et al. Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus. Circulation. 2011;124(4):444-53
240. Terman A, Brunk UT. Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc Res. 2005;68(3):355-65
241. Taneike M, Yamaguchi O, Nakai A, et al. Inhibition of autophagy in the heart induces age-related cardiomyopathy. Autophagy. 2010;6(5):600-6
242. Nakai A, Yamaguchi O, Takeda T, et al. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med. 2007;13(5):619-24
243. Gottlieb RA, Mentzer RM, Jr., Linton PJ. Impaired mitophagy at the heart of injury. Autophagy. 2011;7(12):1573-4
244. Xu X, Hua Y, Nair S, Zhang Y, Ren J. Akt2 knockout preserves cardiac function in high-fat diet-induced obesity by rescuing cardiac autophagosome maturation. J Mol Cell Biol. 2013;5(1):61-3
245. Beauloye C, Marsin AS, Bertrand L, et al. Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides. FEBS Lett. 2001;505(3):348-52
246. Xu X, Kobayashi S, Chen K, et al. Diminished autophagy limits cardiac injury in mouse models of type 1 diabetes. J Biol Chem. 2013;288(25):18077-92
247. van Reyk DM, Gillies MC, Davies MJ. The retina: oxidative stress and diabetes. Redox Rep. 2003;8(4):187-92
248. Pennathur S, Ido Y, Heller JI, et al. Reactive carbonyls and polyunsaturated fatty acids produce a hydroxyl radical-like species: a potential pathway for oxidative damage of retinal proteins in diabetes. J Biol Chem. 2005;280(24):22706-14
249. Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH. Autophagy, exosomes and drusen formation in age-related macular degeneration. Autophagy. 2009;5(4):563-4
250. Kaarniranta K. Autophagy--hot topic in AMD. Acta Ophthalmol. 2010;88(4):387-8
251. Rodríguez-Muela N, Koga H, García-Ledo L, et al. Balance between autophagic pathways preserves retinal homeostasis. Aging Cell. 2013;12(3):478-88
252. Devi TS, Lee I, Huttemann M, Kumar A, Nantwi KD, Singh LP. TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy. Exp Diabetes Res. 2012;2012:438238.