Mitofusins, from Mitochondria to Metabolism

Molecular Cell

Volumn 61, Issue 5, 2016, Pages 683-694

  Schrepfer, Emilie ^a,b   Scorrano, Luca ^a,b  

^a VENETIAN INSTITUTE OF MOLECULAR MEDICINE   (Italy)

^b UNIVERSITY OF PADOVA   (Italy)

Author keywords

Bioenergetic; Mitochondrial dynamics; Mitofusins

Indexed keywords

MITOCHONDRIAL PROTEIN; MITOFUSIN; MITOFUSIN 1; MITOFUSIN 2; UNCLASSIFIED DRUG; CARRIER PROTEIN; GUANOSINE TRIPHOSPHATASE; MFN1 PROTEIN, HUMAN; MFN2 PROTEIN, HUMAN;

AGING; APOPTOSIS; AUTOPHAGY; BIOENERGY; BRAIN; BROWN ADIPOSE TISSUE; CELL CYCLE PROGRESSION; CELL FATE; CYTOARCHITECTURE; DIABETES MELLITUS; HEART MUSCLE; HOMEOSTASIS; HUMAN; MALIGNANT NEOPLASTIC DISEASE; METABOLIC DISORDER; MITOCHONDRIAL RESPIRATION; NONHUMAN; OBESITY; REGULATORY MECHANISM; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; ANIMAL; ENERGY METABOLISM; METABOLISM; MITOCHONDRIAL DYNAMICS; MITOCHONDRION; NEOPLASM; PATHOLOGY;

AGING; ANIMALS; ENERGY METABOLISM; GTP PHOSPHOHYDROLASES; HOMEOSTASIS; HUMANS; METABOLIC DISEASES; MITOCHONDRIA; MITOCHONDRIAL DYNAMICS; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIAL PROTEINS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84959550018     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2016.02.022     Document Type: Review

References (117)

1. Aponte Y., Atasoy D., Sternson S.M. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat. Neurosci. 2011, 14:351-355.
2. Bach D., Pich S., Soriano F.X., Vega N., Baumgartner B., Oriola J., Daugaard J.R., Lloberas J., Camps M., Zierath J.R., et al. Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J. Biol. Chem. 2003, 278:17190-17197.
3. Bach D., Naon D., Pich S., Soriano F.X., Vega N., Rieusset J., Laville M., Guillet C., Boirie Y., Wallberg-Henriksson H., et al. Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6. Diabetes 2005, 54:2685-2693.
4. Boldogh I.R., Pon L.A. Mitochondria on the move. Trends Cell Biol. 2007, 17:502-510.
5. Bonnet S., Archer S.L., Allalunis-Turner J., Haromy A., Beaulieu C., Thompson R., Lee C.T., Lopaschuk G.D., Puttagunta L., Bonnet S., et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 2007, 11:37-51.
6. Bourne H.R., Sanders D.A., McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature 1991, 349:117-127.
7. Cannon B., Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 2004, 84:277-359.
8. Cartoni R., Léger B., Hock M.B., Praz M., Crettenand A., Pich S., Ziltener J.L., Luthi F., Dériaz O., Zorzano A., et al. Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. J. Physiol. 2005, 567:349-358.
9. Cerqua C., Anesti V., Pyakurel A., Liu D., Naon D., Wiche G., Baffa R., Dimmer K.S., Scorrano L. Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition. EMBO Rep. 2010, 11:854-860.
10. Chen Y., Dorn G.W. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 2013, 340:471-475.
11. Chen H., Detmer S.A., Ewald A.J., Griffin E.E., Fraser S.E., Chan D.C. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J. Cell Biol. 2003, 160:189-200.
12. Chen H.Y., Trumbauer M.E., Chen A.S., Weingarth D.T., Adams J.R., Frazier E.G., Shen Z., Marsh D.J., Feighner S.D., Guan X.M., et al. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 2004, 145:2607-2612.
13. Chen K.H., Guo X., Ma D., Guo Y., Li Q., Yang D., Li P., Qiu X., Wen S., Xiao R.P., Tang J. Dysregulation of HSG triggers vascular proliferative disorders. Nat. Cell Biol. 2004, 6:872-883.
14. Chen H., Chomyn A., Chan D.C. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J. Biol. Chem. 2005, 280:26185-26192.
15. Chen H., McCaffery J.M., Chan D.C. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 2007, 130:548-562.
16. Chen H., Vermulst M., Wang Y.E., Chomyn A., Prolla T.A., McCaffery J.M., Chan D.C. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 2010, 141:280-289.
17. Chen Y., Liu Y., Dorn G.W. Mitochondrial fusion is essential for organelle function and cardiac homeostasis. Circ. Res. 2011, 109:1327-1331.
18. Chen K.H., Dasgupta A., Ding J., Indig F.E., Ghosh P., Longo D.L. Role of mitofusin 2 (Mfn2) in controlling cellular proliferation. FASEB J. 2014, 28:382-394.
19. Cheng X., Zhou D., Wei J., Lin J. Cell-cycle arrest at G2/M and proliferation inhibition by adenovirus-expressed mitofusin-2 gene in human colorectal cancer cell lines. Neoplasma 2013, 60:620-626.
20. Chung J.G., Yeh K.T., Wu S.L., Hsu N.Y., Chen G.W., Yeh Y.W., Ho H.C. Novel transmembrane GTPase of non-small cell lung cancer identified by mRNA differential display. Cancer Res. 2001, 61:8873-8879.
21. Cipolat S., Martins de Brito O., Dal Zilio B., Scorrano L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc. Natl. Acad. Sci. USA 2004, 101:15927-15932.
22. Cosson P., Marchetti A., Ravazzola M., Orci L. Mitofusin-2 independent juxtaposition of endoplasmic reticulum and mitochondria: an ultrastructural study. PLoS ONE 2012, 7:e46293.
23. de Brito O.M., Scorrano L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 2008, 456:605-610.
24. de Brito O.M., Scorrano L. Mitofusin 2: a mitochondria-shaping protein with signaling roles beyond fusion. Antioxid. Redox Signal. 2008, 10:621-633.
25. Diaz B., Fuentes-Mera L., Tovar A., Montiel T., Massieu L., Martínez-Rodríguez H.G., Camacho A. Saturated lipids decrease mitofusin 2 leading to endoplasmic reticulum stress activation and insulin resistance in hypothalamic cells. Brain Res. 2015, 1627:80-89.
26. Dietrich M.O., Liu Z.W., Horvath T.L. Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity. Cell 2013, 155:188-199.
27. Ding Y., Gao H., Zhao L., Wang X., Zheng M. Mitofusin 2-deficiency suppresses cell proliferation through disturbance of autophagy. PLoS ONE 2015, 10:e0121328.
28. Eura Y., Ishihara N., Yokota S., Mihara K. Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion. J. Biochem. 2003, 134:333-344.
29. Filadi R., Greotti E., Turacchio G., Luini A., Pozzan T., Pizzo P. Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proc. Natl. Acad. Sci. USA 2015, 112:E2174-E2181.
30. Frank S., Gaume B., Bergmann-Leitner E.S., Leitner W.W., Robert E.G., Catez F., Smith C.L., Youle R.J. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 2001, 1:515-525.
31. Frezza C., Gottlieb E. Mitochondria in cancer: not just innocent bystanders. Semin. Cancer Biol. 2009, 19:4-11.
32. Gao Q., Wang X.M., Ye H.W., Yu Y., Kang P.F., Wang H.J., Guan S.D., Li Z.H. Changes in the expression of cardiac mitofusin-2 in different stages of diabetes in rats. Mol. Med. Rep. 2012, 6:811-814.
33. García-Carrizo F., Nozhenko Y., Palou A., Rodríguez A.M. Leptin Effect on Acetylation and Phosphorylation of Pgc1α in Muscle Cells Associated With Ampk and Akt Activation in High-Glucose Medium. J. Cell. Physiol. 2016, 231:641-649.
34. Gomes L.C., Di Benedetto G., Scorrano L. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat. Cell Biol. 2011, 13:589-598.
35. Gong G., Song M., Csordas G., Kelly D.P., Matkovich S.J., Dorn G.W. Parkin-mediated mitophagy directs perinatal cardiac metabolic maturation in mice. Science 2015, 350:aad2459.
36. Griffin E.E., Chan D.C. Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion. J. Biol. Chem. 2006, 281:16599-16606.
37. Guo X., Chen K.H., Guo Y., Liao H., Tang J., Xiao R.P. Mitofusin 2 triggers vascular smooth muscle cell apoptosis via mitochondrial death pathway. Circ. Res. 2007, 101:1113-1122.
38. Hailey D.W., Rambold A.S., Satpute-Krishnan P., Mitra K., Sougrat R., Kim P.K., Lippincott-Schwartz J. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 2010, 141:656-667.
39. Hamasaki M., Furuta N., Matsuda A., Nezu A., Yamamoto A., Fujita N., Oomori H., Noda T., Haraguchi T., Hiraoka Y., et al. Autophagosomes form at ER-mitochondria contact sites. Nature 2013, 495:389-393.
40. Hernández-Alvarez M.I., Thabit H., Burns N., Shah S., Brema I., Hatunic M., Finucane F., Liesa M., Chiellini C., Naon D., et al. Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1alpha/Mitofusin-2 regulatory pathway in response to physical activity. Diabetes Care 2010, 33:645-651.
41. Hickey F.B., Corcoran J.B., Griffin B., Bhreathnach U., Mortiboys H., Reid H.M., Andrews D., Byrne S., Furlong F., Martin F., et al. IHG-1 increases mitochondrial fusion and bioenergetic function. Diabetes 2014, 63:4314-4325.
42. Hoppins S., Nunnari J. The molecular mechanism of mitochondrial fusion. Biochim. Biophys. Acta 2009, 1793:20-26.
43. Hsu W.H., Lee B.H., Pan T.M. Leptin-induced mitochondrial fusion mediates hepatic lipid accumulation. Int. J. Obes. 2015, 39:1750-1756.
44. Ishihara N., Eura Y., Mihara K. Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. J. Cell Sci. 2004, 117:6535-6546.
45. Jheng H.F., Tsai P.J., Guo S.M., Kuo L.H., Chang C.S., Su I.J., Chang C.R., Tsai Y.S. Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle. Mol. Cell. Biol. 2012, 32:309-319.
46. Jin S.M., Youle R.J. PINK1- and Parkin-mediated mitophagy at a glance. J. Cell Sci. 2012, 125:795-799.
47. Jin B., Fu G., Pan H., Cheng X., Zhou L., Lv J., Chen G., Zheng S. Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma. Med. Oncol. 2011, 28(Suppl 1):S373-S380.
48. Karbowski M., Jeong S.Y., Youle R.J. Endophilin B1 is required for the maintenance of mitochondrial morphology. J. Cell Biol. 2004, 166:1027-1039.
49. Karbowski M., Norris K.L., Cleland M.M., Jeong S.Y., Youle R.J. Role of Bax and Bak in mitochondrial morphogenesis. Nature 2006, 443:658-662.
50. Kelley D.E., He J., Menshikova E.V., Ritov V.B. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002, 51:2944-2950.
51. Koshiba T., Detmer S.A., Kaiser J.T., Chen H., McCaffery J.M., Chan D.C. Structural basis of mitochondrial tethering by mitofusin complexes. Science 2004, 305:858-862.
52. Leboucher G.P., Tsai Y.C., Yang M., Shaw K.C., Zhou M., Veenstra T.D., Glickman M.H., Weissman A.M. Stress-induced phosphorylation and proteasomal degradation of mitofusin 2 facilitates mitochondrial fragmentation and apoptosis. Mol. Cell 2012, 47:547-557.
53. Lee S., Jeong S.Y., Lim W.C., Kim S., Park Y.Y., Sun X., Youle R.J., Cho H. Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence. J. Biol. Chem. 2007, 282:22977-22983.
54. Lee J.Y., Kapur M., Li M., Choi M.C., Choi S., Kim H.J., Kim I., Lee E., Taylor J.P., Yao T.P. MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria. J. Cell Sci. 2014, 127:4954-4963.
55. Lionetti L., Mollica M.P., Donizzetti I., Gifuni G., Sica R., Pignalosa A., Cavaliere G., Gaita M., De Filippo C., Zorzano A., Putti R. High-lard and high-fish-oil diets differ in their effects on function and dynamic behaviour of rat hepatic mitochondria. PLoS ONE 2014, 9:e92753.
56. Liu R., Jin P., Yu L., Wang Y., Han L., Shi T., Li X. Impaired mitochondrial dynamics and bioenergetics in diabetic skeletal muscle. PLoS ONE 2014, 9:e92810.
57. Loiseau D., Chevrollier A., Verny C., Guillet V., Gueguen N., Pou de Crescenzo M.A., Ferré M., Malinge M.C., Guichet A., Nicolas G., et al. Mitochondrial coupling defect in Charcot-Marie-Tooth type 2A disease. Ann. Neurol. 2007, 61:315-323.
58. Low H.H., Löwe J. A bacterial dynamin-like protein. Nature 2006, 444:766-769.
59. Low H.H., Sachse C., Amos L.A., Löwe J. Structure of a bacterial dynamin-like protein lipid tube provides a mechanism for assembly and membrane curving. Cell 2009, 139:1342-1352.
60. MacAskill A.F., Kittler J.T. Control of mitochondrial transport and localization in neurons. Trends Cell Biol. 2010, 20:102-112.
61. Malka F., Guillery O., Cifuentes-Diaz C., Guillou E., Belenguer P., Lombès A., Rojo M. Separate fusion of outer and inner mitochondrial membranes. EMBO Rep. 2005, 6:853-859.
62. Mingrone G., Manco M., Calvani M., Castagneto M., Naon D., Zorzano A. Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity?. Diabetologia 2005, 48:2108-2114.
63. Mishra P., Carelli V., Manfredi G., Chan D.C. Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metab. 2014, 19:630-641.
64. Misko A.L., Sasaki Y., Tuck E., Milbrandt J., Baloh R.H. Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration. J. Neurosci. 2012, 32:4145-4155.
65. Mitra K., Wunder C., Roysam B., Lin G., Lippincott-Schwartz J. A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase. Proc. Natl. Acad. Sci. USA 2009, 106:11960-11965.
66. Molina A.J., Wikstrom J.D., Stiles L., Las G., Mohamed H., Elorza A., Walzer G., Twig G., Katz S., Corkey B.E., Shirihai O.S. Mitochondrial networking protects beta-cells from nutrient-induced apoptosis. Diabetes 2009, 58:2303-2315.
67. Mourier A., Motori E., Brandt T., Lagouge M., Atanassov I., Galinier A., Rappl G., Brodesser S., Hultenby K., Dieterich C., Larsson N.G. Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J. Cell Biol. 2015, 208:429-442.
68. Mozdy A.D., Shaw J.M. A fuzzy mitochondrial fusion apparatus comes into focus. Nat. Rev. Mol. Cell Biol. 2003, 4:468-478.
69. Naon D., Scorrano L. At the right distance: ER-mitochondria juxtaposition in cell life and death. Biochim. Biophys. Acta 2014, 1843:2184-2194.
70. Nie Q., Wang C., Song G., Ma H., Kong D., Zhang X., Gan K., Tang Y. Mitofusin 2 deficiency leads to oxidative stress that contributes to insulin resistance in rat skeletal muscle cells. Mol. Biol. Rep. 2014, 41:6975-6983.
71. Nisoli E., Tonello C., Cardile A., Cozzi V., Bracale R., Tedesco L., Falcone S., Valerio A., Cantoni O., Clementi E., et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 2005, 310:314-317.
72. Olichon A., Emorine L.J., Descoins E., Pelloquin L., Brichese L., Gas N., Guillou E., Delettre C., Valette A., Hamel C.P., et al. The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett. 2002, 523:171-176.
73. Papanicolaou K.N., Khairallah R.J., Ngoh G.A., Chikando A., Luptak I., O'Shea K.M., Riley D.D., Lugus J.J., Colucci W.S., Lederer W.J., et al. Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol. Cell. Biol. 2011, 31:1309-1328.
74. Papanicolaou K.N., Kikuchi R., Ngoh G.A., Coughlan K.A., Dominguez I., Stanley W.C., Walsh K. Mitofusins 1 and 2 are essential for postnatal metabolic remodeling in heart. Circ. Res. 2012, 111:1012-1026.
75. Park Y.Y., Cho H. Mitofusin 1 is degraded at G2/M phase through ubiquitylation by MARCH5. Cell Div. 2012, 7:25.
76. Park Y.Y., Lee S., Karbowski M., Neutzner A., Youle R.J., Cho H. Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1. J. Cell Sci. 2010, 123:619-626.
77. Patti M.E., Butte A.J., Crunkhorn S., Cusi K., Berria R., Kashyap S., Miyazaki Y., Kohane I., Costello M., Saccone R., 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. USA 2003, 100:8466-8471.
78. Peng C., Rao W., Zhang L., Wang K., Hui H., Wang L., Su N., Luo P., Hao Y.L., Tu Y., et al. Mitofusin 2 ameliorates hypoxia-induced apoptosis via mitochondrial function and signaling pathways. Int. J. Biochem. Cell Biol. 2015, 69:29-40.
79. Pernas L., Scorrano L. Mito-Morphosis: Mitochondrial Fusion, Fission, and Cristae Remodeling as Key Mediators of Cellular Function. Annu. Rev. Physiol. 2015, 78:505-531.
80. Petersen K.F., Dufour S., Befroy D., Garcia R., Shulman G.I. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N. Engl. J. Med. 2004, 350:664-671.
81. Pich S., Bach D., Briones P., Liesa M., Camps M., Testar X., Palacín M., Zorzano A. The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum. Mol. Genet. 2005, 14:1405-1415.
82. Pyakurel A., Savoia C., Hess D., Scorrano L. Extracellular regulated kinase phosphorylates mitofusin 1 to control mitochondrial morphology and apoptosis. Mol. Cell 2015, 58:244-254.
83. Rambold A.S., Kostelecky B., Elia N., Lippincott-Schwartz J. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc. Natl. Acad. Sci. USA 2011, 108:10190-10195.
84. Rambold A.S., Cohen S., Lippincott-Schwartz J. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell 2015, 32:678-692.
85. Rehman J., Zhang H.J., Toth P.T., Zhang Y., Marsboom G., Hong Z., Salgia R., Husain A.N., Wietholt C., Archer S.L. Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB J. 2012, 26:2175-2186.
86. Rojo M., Legros F., Chateau D., Lombès A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J. Cell Sci. 2002, 115:1663-1674.
87. Santel A., Frank S., Gaume B., Herrler M., Youle R.J., Fuller M.T. Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J. Cell Sci. 2003, 116:2763-2774.
88. Schick M. Membrane fusion: the emergence of a new paradigm. J. Stat. Phys. 2011, 142:1317-1323.
89. Schieke S.M., McCoy J.P., Finkel T. Coordination of mitochondrial bioenergetics with G1 phase cell cycle progression. Cell Cycle 2008, 7:1782-1787.
90. Schneeberger M., Dietrich M.O., Sebastián D., Imbernón M., Castaño C., Garcia A., Esteban Y., Gonzalez-Franquesa A., Rodríguez I.C., Bortolozzi A., et al. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell 2013, 155:172-187.
91. Scorrano L. Keeping mitochondria in shape: a matter of life and death. Eur. J. Clin. Invest. 2013, 43:886-893.
92. Sebastián D., Hernández-Alvarez M.I., Segalés J., Sorianello E., Muñoz J.P., Sala D., Waget A., Liesa M., Paz J.C., Gopalacharyulu P., et al. Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc. Natl. Acad. Sci. USA 2012, 109:5523-5528.
93. Segalés J., Paz J.C., Hernández-Alvarez M.I., Sala D., Muñoz J.P., Noguera E., Pich S., Palacín M., Enríquez J.A., Zorzano A. A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells. Am. J. Physiol. Endocrinol. Metab. 2013, 305:E1208-E1221.
94. Shen T., Zheng M., Cao C., Chen C., Tang J., Zhang W., Cheng H., Chen K.H., Xiao R.P. Mitofusin-2 is a major determinant of oxidative stress-mediated heart muscle cell apoptosis. J. Biol. Chem. 2007, 282:23354-23361.
95. Short K.R., Bigelow M.L., Kahl J., Singh R., Coenen-Schimke J., Raghavakaimal S., Nair K.S. Decline in skeletal muscle mitochondrial function with aging in humans. Proc. Natl. Acad. Sci. USA 2005, 102:5618-5623.
96. Shutt T., Geoffrion M., Milne R., McBride H.M. The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep. 2012, 13:909-915.
97. Song Z., Ghochani M., McCaffery J.M., Frey T.G., Chan D.C. Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. Mol. Biol. Cell 2009, 20:3525-3532.
98. Sood A., Jeyaraju D.V., Prudent J., Caron A., Lemieux P., McBride H.M., Laplante M., Tóth K., Pellegrini L. A Mitofusin-2-dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver. Proc. Natl. Acad. Sci. USA 2014, 111:16017-16022.
99. Soriano F.X., Liesa M., Bach D., Chan D.C., Palacín M., Zorzano A. Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2. Diabetes 2006, 55:1783-1791.
100. Sugiura A., Nagashima S., Tokuyama T., Amo T., Matsuki Y., Ishido S., Kudo Y., McBride H.M., Fukuda T., Matsushita N., et al. MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. Mol. Cell 2013, 51:20-34.
101. Szabadkai G., Simoni A.M., Chami M., Wieckowski M.R., Youle R.J., Rizzuto R. Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+-mediated apoptosis. Mol. Cell 2004, 16:59-68.
102. Taguchi N., Ishihara N., Jofuku A., Oka T., Mihara K. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J. Biol. Chem. 2007, 282:11521-11529.
103. Toledo F.G., Watkins S., Kelley D.E. Changes induced by physical activity and weight loss in the morphology of intermyofibrillar mitochondria in obese men and women. J. Clin. Endocrinol. Metab. 2006, 91:3224-3227.
104. Tubbs E., Theurey P., Vial G., Bendridi N., Bravard A., Chauvin M.A., Ji-Cao J., Zoulim F., Bartosch B., Ovize M., et al. Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance. Diabetes 2014, 63:3279-3294.
105. Vance J.E. MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochim. Biophys. Acta 2014, 1841:595-609.
106. Wang W., Zhu F., Wang S., Wei J., Jia C., Zhang Y., Zhou L., Xie H., Zheng S. HSG provides antitumor efficacy on hepatocellular carcinoma both in vitro and in vivo. Oncol. Rep. 2010, 24:183-188.
107. Wang W., Xie Q., Zhou X., Yao J., Zhu X., Huang P., Zhang L., Wei J., Xie H., Zhou L., Zheng S. Mitofusin-2 triggers mitochondria Ca2+ influx from the endoplasmic reticulum to induce apoptosis in hepatocellular carcinoma cells. Cancer Lett. 2015, 358:47-58.
108. Wikstrom J.D., Mahdaviani K., Liesa M., Sereda S.B., Si Y., Las G., Twig G., Petrovic N., Zingaretti C., Graham A., et al. Hormone-induced mitochondrial fission is utilized by brown adipocytes as an amplification pathway for energy expenditure. EMBO J. 2014, 33:418-436.
109. Wu Z., Puigserver P., Andersson U., Zhang C., Adelmant G., Mootha V., Troy A., Cinti S., Lowell B., Scarpulla R.C., Spiegelman B.M. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 1999, 98:115-124.
110. Yoon Y.S., Yoon D.S., Lim I.K., Yoon S.H., Chung H.Y., Rojo M., Malka F., Jou M.J., Martinou J.C., Yoon G. Formation of elongated giant mitochondria in DFO-induced cellular senescence: involvement of enhanced fusion process through modulation of Fis1. J. Cell. Physiol. 2006, 209:468-480.
111. Youle R.J., Narendra D.P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 2011, 12:9-14.
112. Zhang G.E., Jin H.L., Lin X.K., Chen C., Liu X.S., Zhang Q., Yu J.R. Anti-tumor effects of Mfn2 in gastric cancer. Int. J. Mol. Sci. 2013, 14:13005-13021.
113. Zhang X., Wang C., Song G., Gan K., Kong D., Nie Q., Ren L. Mitofusion-2-mediated alleviation of insulin resistance in rats through reduction in lipid intermediate accumulation in skeletal muscle. J. Biomed. Sci. 2013, 20:45.
114. Zhang W., Shu C., Li Q., Li M., Li X. Adiponectin affects vascular smooth muscle cell proliferation and apoptosis through modulation of the mitofusin-2-mediated Ras-Raf-Erk1/2 signaling pathway. Mol. Med. Rep. 2015, 12:4703-4707.
115. Zhao T., Huang X., Han L., Wang X., Cheng H., Zhao Y., Chen Q., Chen J., Cheng H., Xiao R., Zheng M. Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes. J. Biol. Chem. 2012, 287:23615-23625.
116. Zhao N., Zhang Y., Liu Q., Xiang W. Mfn2 Affects Embryo Development via Mitochondrial Dysfunction and Apoptosis. PLoS ONE 2015, 10:e0125680.
117. Züchner S., Mersiyanova I.V., Muglia M., Bissar-Tadmouri N., Rochelle J., Dadali E.L., Zappia M., Nelis E., Patitucci A., Senderek J., et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat. Genet. 2004, 36:449-451.