The critical roles of mitophagy in cerebral ischemia

Protein and Cell

Volumn 7, Issue 10, 2016, Pages 699-713

  Tang, Yan Cheng ^a   Tian, Hong Xia ^b   Yi, Tao ^a   Chen, Hu Biao ^a  

^a HONG KONG BAPTIST UNIVERSITY   (Hong Kong)

^b GUANGDONG PROVINCIAL PEOPLE'S HOSPITAL   (China)

Author keywords

autophagy; cerebral ischemia; mitochondria; mitophagy

Indexed keywords

PARKIN; REACTIVE OXYGEN METABOLITE;

BLOOD FLOW; BRAIN ISCHEMIA; CALCIUM HOMEOSTASIS; CEREBROVASCULAR ACCIDENT; FLUORESCENCE MICROSCOPY; HUMAN; MITOCHONDRIAL DNA REPLICATION; MITOPHAGY; MITOTYPE; NONHUMAN; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; METABOLISM; PATHOLOGY;

ANIMALS; BRAIN ISCHEMIA; HUMANS; MITOCHONDRIAL DEGRADATION; REACTIVE OXYGEN SPECIES; STROKE;

EID: 84983427033     PISSN: 1674800X     EISSN: 16748018     Source Type: Journal    
DOI: 10.1007/s13238-016-0307-0     Document Type: Review

References (128)

1. Aerbajinai W, Giattina M, Lee YT, Raffeld M, Miller JL (2003) The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation. Blood 102:712–717
2. Ashford TP, Porter KR (1962) Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12:198–202
3. Baek SH, Noh AR, Kim KA, Akram M, Shin YJ, Kim ES, Yu SW, Majid A, Bae ON (2014) Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Stroke 45:2438–2443
4. Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J, Mazure NM (2009) Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29:2570–2581
5. Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song QH, Foreman O, Kirkpatrick DS, Sheng MG (2014) The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 510:370–375
6. Birse-Archbold JL, Kerr LE, Jones PA, McCulloch J, Sharkey J (2005) Differential profile of Nix upregulation and translocation during hypoxia/ischaemia in vivo versus in vitro. J Cereb Blood Flow Metab 25:1356–1365
7. Bruick RK (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci USA 97:9082–9087
8. Carden DL, Granger DN (2000) Pathophysiology of ischaemia–reperfusion injury. J Pathol 190:255–266
9. Carloni S, Girelli S, Scopa C, Buonocore G, Longini M, Balduini W (2010) Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy 6:366–377
10. Casley CS, Canevari L, Land JM, Clark JB, Sharpe MA (2002) Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J Neurochem 80:91–100
11. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL, Hess S, Chan DC (2011) Broad activation of the ubiquitin–proteasome system by Parkin is critical for mitophagy. Hum Mol Genet 20:1726–1737
12. Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14
13. Chaugule VK, Burchell L, Barber KR, Sidhu A, Leslie SJ, Shaw GS, Walden H (2011) Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J 30:2853–2867
14. Chen G, Cizeau J, Vande Velde C, Park JH, Bozek G, Bolton J, Shi L, Dubik D, Greenberg A (1999) Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins. J Biol Chem 274:7–10
15. Chen G, Han Z, Feng D, Chen Y, Chen L, Wu H, Huang L, Zhou C, Cai X, Fu C et al (2014) A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol Cell 54:362–377
16. Chen H, Chan DC (2010) Physiological functions of mitochondrial fusion. Ann NY Acad Sci 1201:21–25
17. Chen M, Chen Z, Wang Y, Tan Z, Zhu C, Li Y, Han Z, Chen L, Gao R, Liu L et al (2016) Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy. Autophagy 12:689–702
18. Chen Y, Dorn GW II (2013) PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340:471–475
19. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162–1166
20. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127:59–69
21. Deas E, Wood NW, Plun-Favreau H (2011) Mitophagy and Parkinson’s disease: the PINK1-parkin link. Biochim Biophys Acta 1813:623–633
22. Deter RL, Baudhuin P, De Duve C (1967) Participation of lysosomes in cellular autophagy induced in rat liver by glucagon. J Cell Biol 35:C11–C16
23. Deter RL, De Duve C (1967) Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J Cell Biol 33:437–449
24. Di Y, He YL, Zhao T, Huang X, Wu KW, Liu SH, Zhao YQ, Fan M, Wu LY, Zhu LL (2015) Methylene blue reduces acute cerebral ischemic injury via the induction of mitophagy. Mol Med 21:420–429
25. Ding WX, Yin XM (2012) Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem 393:547–564
26. Ding WX, Ni HM, Li M, Liao Y, Chen X, Stolz DB, Dorn GW II, Yin XM (2010) Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem 285:27879–27890
27. Diwan A, Koesters AG, Odley AM, Pushkaran S, Baines CP, Spike BT, Daria D, Jegga AG, Geiger H, Aronow BJ et al (2007) Unrestrained erythroblast development in Nix−/− mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci USA 104:6794–6799
28. Dolman NJ, Chambers KM, Mandavilli B, Batchelor RH, Janes MS (2013) Tools and techniques to measure mitophagy using fluorescence microscopy. Autophagy 9:1653–1662
29. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R et al (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331:456–461
30. Frank M, Duvezin-Caubet S, Koob S, Occhipinti A, Jagasia R, Petcherski A, Ruonala MO, Priault M, Salin B, Reichert AS (2012) Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner. Biochim Biophys Acta 1823:2297–2310
31. Galvez AS, Brunskill EW, Marreez Y, Benner BJ, Regula KM, Kirschenbaum LA, Dorn GW II (2006) Distinct pathways regulate proapoptotic Nix and BNip3 in cardiac stress. J Biol Chem 281:1442–1448
32. Gao D, Kawai N, Nakamura T, Lu F, Fei Z, Tamiya T (2013) Anti-inflammatory effect of d-allose in cerebral ischemia/reperfusion injury in rats. Neurol Med Chir (Tokyo) 53:365–374
33. Gomes LC, Di Benedetto G, Scorrano L (2011) During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 13:589–598
34. Gurung P, Lukens JR, Kanneganti TD (2015) Mitochondria: diversity in the regulation of the NLRP3 inflammasome. Trends Mol Med 21:193–201
35. Hollville E, Carroll RG, Cullen SP, Martin SJ (2014) Bcl-2 family proteins participate in mitochondrial quality control by regulating Parkin/PINK1-dependent mitophagy. Mol Cell 55:451–466
36. Hoshino A, Matoba S, Iwai-Kanai E, Nakamura H, Kimata M, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y et al (2012) p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. J Mol Cell Cardiol 52:175–184
37. James DI, Parone PA, Mattenberger Y, Martinou JC (2003) hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem 278:36373–36379
38. Jin R, Yang G, Li G (2010a) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87:779–789
39. Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ (2010b) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191:933–942
40. Kageyama Y, Hoshijima M, Seo K, Bedja D, Sysa-Shah P, Andrabi SA, Chen W, Hoke A, Dawson VL, Dawson TM et al (2014) Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain. EMBO J 33:2798–2813
41. Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205:143–153
42. Kanki T (2010) Nix, a receptor protein for mitophagy in mammals. Autophagy 6:433–435
43. Katayama H, Kogure T, Mizushima N, Yoshimori T, Miyawaki A (2011) A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. Chem Biol 18:1042–1052
44. Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K, Alessi DR, Knebel A, Trost M, Muqit MM (2014) Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J 460:127–139
45. Kim JY, Cho JJ, Ha J, Park JH (2002) The carboxy terminal C-tail of BNip3 is crucial in induction of mitochondrial permeability transition in isolated mitochondria. Arch Biochem Biophys 398:147–152
46. Kim Y, Park J, Kim S, Song S, Kwon SK, Lee SH, Kitada T, Kim JM, Chung J (2008) PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun 377:975–980
47. Kissova I, Deffieu M, Manon S, Camougrand N (2004) Uth1p is involved in the autophagic degradation of mitochondria. J Biol Chem 279:39068–39074
48. Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, Waguri S, Kawahara N, Kuida K, Nagata S, Kominami E et al (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol 172: 454-469
49. Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R, Burchell L, Walden H, Macartney TJ, Deak M et al (2012) PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol 2:120080
50. Kumar A, Aguirre JD, Condos TE, Martinez-Torres RJ, Chaugule VK, Toth R, Sundaramoorthy R, Mercier P, Knebel A, Spratt DE et al (2015) Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis. EMBO J 34:2506–2521
51. Kumari S, Anderson L, Farmer S, Mehta SL, Li PA (2012) Hyperglycemia alters mitochondrial fission and fusion proteins in mice subjected to cerebral ischemia and reperfusion. Transl Stroke Res 3:296–304
52. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–314
53. Lee S, Zhang C, Liu X (2015) Role of glucose metabolism and ATP in maintaining PINK1 levels during Parkin-mediated mitochondrial damage responses. J Biol Chem 290:904–917
54. Lemasters JJ (2005) Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 8:3–5
55. Li J, Ma X, Yu W, Lou Z, Mu D, Wang Y, Shen B, Qi S (2012) Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats. PLoS One 7:e46498
56. Li Q, Zhang T, Wang J, Zhang Z, Zhai Y, Yang GY, Sun X (2014) Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke. Biochem Biophys Res Commun 444:182–188
57. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568
58. Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W et al (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14:177–185
59. Loson OC, Song Z, Chen H, Chan DC (2013) Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 24:659–667
60. Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F, Juin P, Tasdemir E, Pierron G, Troulinaki K, Tavernarakis N et al (2007) Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J 26:2527–2539
61. Malagelada C, Jin ZH, Jackson-Lewis V, Przedborski S, Greene LA (2010) Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson’s disease. J Neurosci 30:1166–1175
62. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J et al (2007) FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6:458–471
63. Matheoud D, Sugiura A, Bellemare-Pelletier A, Laplante A, Rondeau C, Chemali M, Fazel A, Bergeron JJ, Trudeau LE, Burelle Y et al (2016) Parkinson’s disease-related proteins PINK1 and Parkin repress mitochondrial antigen presentation. Cell 166:314–327
64. Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F et al (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189:211–221
65. McColl BW, Rothwell NJ, Allan SM (2007) Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. J Neurosci 27:4403–4412
66. Mehta SL, Kumari S, Mendelev N, Li PA (2012) Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. BMC Neurosci 13:79
67. Meloni BP, Meade AJ, Kitikomolsuk D, Knuckey NW (2011) Characterisation of neuronal cell death in acute and delayed in vitro ischemia (oxygen-glucose deprivation) models. J Neurosci Methods 195:67–74
68. Mengesdorf T, Jensen PH, Mies G, Aufenberg C, Paschen W (2002) Down-regulation of parkin protein in transient focal cerebral ischemia: a link between stroke and degenerative disease? Proc Natl Acad Sci USA 99:15042–15047
69. Miclescu A, Sharma HS, Martijn C, Wiklund L (2010) Methylene blue protects the cortical blood–brain barrier against ischemia/reperfusion-induced disruptions. Crit Care Med 38:2199–2206
70. Mills EL, O’Neill LA (2016) Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal. Eur J Immunol 46:13–21
71. Minton K (2016) Inflammasome: anti-inflammatory effect of mitophagy. Nat Rev Immunol 16:206
72. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741
73. Murakawa T, Yamaguchi O, Hashimoto A, Hikoso S, Takeda T, Oka T, Yasui H, Ueda H, Akazawa Y, Nakayama H et al (2015) Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nat Commun 6:7527
74. Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803
75. Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ (2010a) p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 6:1090–1106
76. Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010b) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8:e1000298
77. Nezich CL, Wang C, Fogel AI, Youle RJ (2015) MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5. J Cell Biol 210:435–450
78. Nguyen TN, Padman BS, Lazarou M (2016) Deciphering the molecular signals of PINK1/Parkin mitophagy. Trends Cell Biol. doi:10.1016/j.tcb.2016.05.008
79. Okatsu K, Saisho K, Shimanuki M, Nakada K, Shitara H, Sou YS, Kimura M, Sato S, Hattori N, Komatsu M et al (2010) p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells 15:887–900
80. Ordureau A, Harper JW (2014) Cell biology: balancing act. Nature 510:347–348
81. Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K (2010) Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J Cell Biol 191:1141–1158
82. Palencia G, Medrano JA, Ortiz-Plata A, Farfan DJ, Sotelo J, Sanchez A, Trejo-Solis C (2015) Anti-apoptotic, anti-oxidant, and anti-inflammatory effects of thalidomide on cerebral ischemia/reperfusion injury in rats. J Neurol Sci 351:78–87
83. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131–24145
84. Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM et al (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441:1157–1161
85. Plotnikov EY, Vasileva AK, Arkhangelskaya AA, Pevzner IB, Skulachev VP, Zorov DB (2008) Interrelations of mitochondrial fragmentation and cell death under ischemia/reoxygenation and UV-irradiation: protective effects of SkQ1, lithium ions and insulin. FEBS Lett 582:3117–3124
86. Prestigiacomo CJ, Kim SC, Connolly ES, Liao H, Yan S-F, Pinsky DJ (1999) CD18-mediated neutrophil recruitment contributes to the pathogenesis of reperfused but not nonreperfused stroke. Stroke 30:1110–1117
87. Riley BE, Lougheed JC, Callaway K, Velasquez M, Brecht E, Nguyen L, Shaler T, Walker D, Yang Y, Regnstrom K et al (2013) Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases. Nat Commun 4:1982
88. Ritter LS, Orozco JA, Coull BM, McDonagh PF (2000) Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke. Stroke 31:1153–1161
89. Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454:232–235
90. Sauve V, Lilov A, Seirafi M, Vranas M, Rasool S, Kozlov G, Sprules T, Wang J, Trempe JF, Gehring K (2015) A Ubl/ubiquitin switch in the activation of Parkin. EMBO J 34:2492–2505
91. Scherz-Shouval R, Elazar Z (2011) Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci 36:30–38
92. Schmidt-Kastner R, Aguirre-Chen C, Kietzmann T, Saul I, Busto R, Ginsberg MD (2004) Nuclear localization of the hypoxia-regulated pro-apoptotic protein BNIP3 after global brain ischemia in the rat hippocampus. Brain Res 1001:133–142
93. Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832
94. Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL et al (2007) NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 104:19500–19505
95. Shen Q, Du F, Huang S, Rodriguez P, Watts LT, Duong TQ (2013) Neuroprotective efficacy of methylene blue in ischemic stroke: an MRI study. PLoS One 8:e79833
96. Shen Q, Yamano K, Head BP, Kawajiri S, Cheung JT, Wang C, Cho JH, Hattori N, Youle RJ, van der Bliek AM (2014) Mutations in Fis1 disrupt orderly disposal of defective mitochondria. Mol Biol Cell 25:145–159
97. Shi RY, Zhu SH, Li V, Gibson SB, Xu XS, Kong JM (2014) BNIP3 interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke. CNS Neurosci Ther 20:1045–1055
98. Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N (2012) PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep 2:1002
99. Sinha K, Chaudhary G, Gupta YK (2002) Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci 71:655–665
100. Strowig T, Henao-Mejia J, Elinav E, Flavell R (2012) Inflammasomes in health and disease. Nature 481:278–286
101. Sun N, Yun J, Liu J, Malide D, Liu C, Rovira II, Holmstrom KM, Fergusson MM, Yoo YH, Combs CA et al (2015) Measuring in vivo mitophagy. Mol Cell 60:685–696
102. Taanman JW (1999) The mitochondrial genome: structure, transcription, translation and replication. Biochim Biophys Acta 1410:103–123
103. Takagi H, Matsui Y, Hirotani S, Sakoda H, Asano T, Sadoshima J (2007) AMPK mediates autophagy during myocardial ischemia in vivo. Autophagy 3:405–407
104. Tal R, Winter G, Ecker N, Klionsky DJ, Abeliovich H (2007) Aup1p, a yeast mitochondrial protein phosphatase homolog, is required for efficient stationary phase mitophagy and cell survival. J Biol Chem 282:5617–5624
105. Tian F, Deguchi K, Yamashita T, Ohta Y, Morimoto N, Shang J, Zhang X, Liu N, Ikeda Y, Matsuura T et al (2010) In vivo imaging of autophagy in a mouse stroke model. Autophagy 6:1107–1114
106. Toyama EQ, Herzig S, Courchet J, Lewis TL Jr, Loson OC, Hellberg K, Young NP, Chen H, Polleux F, Chan DC et al (2016) Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 351:275–281
107. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G et al (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27:433–446
108. Violot S, Carpentier P, Blanchoin L, Bourgeois D (2009) Reverse pH-dependence of chromophore protonation explains the large stokes shift of the red fluorescent protein mKeima. J Am Chem Soc 131:10356–10357
109. Wang R, Liu YY, Liu XY, Jia SW, Zhao J, Cui D, Wang L (2014) Resveratrol protects neurons and the myocardium by reducing oxidative stress and ameliorating mitochondria damage in a cerebral ischemia rat model. Cell Physiol Biochem 34:854–864
110. Wauer T, Komander D (2013) Structure of the human Parkin ligase domain in an autoinhibited state. EMBO J 32:2099–2112
111. Wauer T, Simicek M, Schubert A, Komander D (2015) Mechanism of phospho-ubiquitin-induced PARKIN activation. Nature 524:370–374
112. Wen Y, Li W, Poteet EC, Xie L, Tan C, Yan LJ, Ju X, Liu R, Qian H, Marvin MA et al (2011) Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem 286:16504–16515
113. Wu W, Tian W, Hu Z, Chen G, Huang L, Li W, Zhang X, Xue P, Zhou C, Liu L et al (2014) ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep 15:566–575
114. Wu W, Li W, Chen H, Jiang L, Zhu R, Feng D (2016) FUNDC1 is a novelx mitochondrial-associated-membrane (MAM) protein required for hypoxia-induced mitochondrial fission and mitophagy. Autophagy 1–2
115. Yamamori T, Ike S, Bo T, Sasagawa T, Sakai Y, Suzuki M, Yamamoto K, Nagane M, Yasui H, Inanami O (2015) Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after X-irradiation. Mol Biol Cell 26:4607–4617
116. Yan WJ, Dong HL, Xiong LZ (2013) The protective roles of autophagy in ischemic preconditioning. Acta Pharmacol Sin 34:636–643
117. Yoshida S, Abe K, Busto R, Watson BD, Kogure K, Ginsberg MD (1982) Influence of transient ischemia on lipid-soluble antioxidants, free fatty-acids and energy metabolites in rat-brain. Brain Res 245:307–316
118. Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12:9–14
119. Zhang RL, Chopp M, Jiang N, Tang WX, Prostak J, Manning AM, Anderson DC (1995) Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke 26:1438–1442; discussion 1443
120. Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283:10892–10903
121. Zhang J, Loyd MR, Randall MS, Waddell MB, Kriwacki RW, Ney PA (2012) A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes. Autophagy 8:1325–1332
122. Zhang X, Yan H, Yuan Y, Gao J, Shen Z, Cheng Y, Shen Y, Wang R-R, Wang X, Hu W-W et al (2013) Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy 9:1321–1333
123. Zhang X, Yuan Y, Jiang L, Zhang J, Gao J, Shen Z, Zheng Y, Deng T, Yan H, Li W et al (2014) Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury: involvement of PARK2-dependent mitophagy. Autophagy 10:1801–1813
124. Zhao J, Mou Y, Bernstock JD, Klimanis D, Wang S, Spatz M, Maric D, Johnson K, Klinman DM, Li X et al (2015) Synthetic oligodeoxynucleotides containing multiple telemeric TTAGGG motifs suppress inflammasome activity in macrophages subjected to oxygen and glucose deprivation and reduce ischemic brain injury in stroke-prone spontaneously hypertensive rats. PLoS One 10:e0140772
125. Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins G, Ali SR et al (2016) NF-kappaB restricts inflammasome activation via elimination of damaged mitochondria. Cell 164:896–910
126. Zhu J, Dagda RK, Chu CT (2011) Monitoring mitophagy in neuronal cell cultures. Methods Mol Biol 793:325–339
127. Zuo W, Zhang S, Xia CY, Guo XF, He WB, Chen NH (2014) Mitochondria autophagy is induced after hypoxic/ischemic stress in a Drp1 dependent manner: the role of inhibition of Drp1 in ischemic brain damage. Neuropharmacology 86:103–115
128. Zuo W, Yang PF, Chen J, Zhang Z, Chen NH (2016) Drp-1, a potential therapeutic target for brain ischemic stroke. Br J Pharmacol 173:1665–1677