Two Rare Human Mitofusin 2 Mutations Alter Mitochondrial Dynamics and Induce Retinal and Cardiac Pathology in Drosophila

PLoS ONE

Volumn 7, Issue 9, 2012, Pages

  Eschenbacher, William H ^a   Song, Moshi ^a   Chen, Yun ^a   Bhandari, Poonam ^a   Zhao, Peter ^a   Jowdy, Casey C ^a   Engelhard, John T ^a   Dorn II, Gerald W ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; GLUTAMINE; ISOLEUCINE; MESSENGER RNA; METHIONINE; MITOFUSIN 2;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOINFORMATICS; CONTROLLED STUDY; DROSOPHILA; EMBRYO; EXOME; FIBROBLAST; GENE EXPRESSION; HEART DILATATION; HEART DISEASE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MITOCHONDRIAL MEMBRANE; MOLECULAR DYNAMICS; MOUSE; MUTATIONAL ANALYSIS; NONHUMAN; PHENOTYPE; PROTEIN DOMAIN; PROTEIN EXPRESSION; RETINA DISEASE; RNA INTERFERENCE; SEQUENCE ANALYSIS; WILD TYPE;

ANIMALS; BASE SEQUENCE; COMPUTATIONAL BIOLOGY; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; FIBROBLASTS; GTP PHOSPHOHYDROLASES; HUMANS; MEMBRANE PROTEINS; MICE; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MODELS, GENETIC; MOLECULAR SEQUENCE DATA; MUTATION; MYOCARDIUM; PHENOTYPE; RECOMBINANT PROTEINS; RETINA; SEQUENCE HOMOLOGY, NUCLEIC ACID;

MURINAE;

EID: 84866049277     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0044296     Document Type: Article

References (43)

1. Tatsuta T, Langer T, (2008) Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J 27: 306-314.
2. Westermann B, (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11: 872-884.
3. Malka F, Guillery O, Cifuentes-Diaz C, Guillou E, Belenguer P, et al. (2005) Separate fusion of outer and inner mitochondrial membranes. EMBO Rep 6: 853-859.
4. Song Z, Ghochani M, McCaffery JM, Frey TG, Chan DC, (2009) Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. Mol Biol Cell 20: 3525-3532.
5. Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, et al. (2004) Structural basis of mitochondrial tethering by mitofusin complexes. Science 305: 858-862.
6. Griffin EE, Detmer SA, Chan DC, (2006) Molecular mechanism of mitochondrial membrane fusion. Biochim Biophys Acta 1763: 482-489.
7. Griffin EE, Chan DC, (2006) Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion. J Biol Chem 281: 16599-16606.
8. Chen H, Chomyn A, Chan DC, (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280: 26185-26192.
9. Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, et al. (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160: 189-200.
10. Chen H, McCaffery JM, Chan DC, (2007) Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130: 548-562.
11. Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA, et al. (2010) Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141: 280-289.
12. Chen Y, Liu Y, Dorn GW 2nd (2011) Mitochondrial Fusion is Essential for Organelle Function and Cardiac Homeostasis. Circ Res 109: 1327-1331.
13. Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, et al. (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36: 449-451.
14. Verhoeven K, Claeys KG, Zuchner S, Schroder JM, Weis J, et al. (2006) MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain 129: 2093-2102.
15. Yoshida H, Inagaki M, Shukuya M, Ono S, Shimizu N, et al. (1991) [Charcot-Marie-Tooth disease associated with dilated cardiomyopathy: an autopsy case report]. Kokyu to junkan Respiration & circulation 39: 295-298.
16. Sevillano Fernandez JA, Paz Fraile A, Cano Ballesteros JC, Villalba Garcia MV, Otero Perez R, et al. (1994) [Charcot-Marie-Tooth disease, dilated myocardiopathy and cardiac conduction disorders]. Anales de medicina interna 11: 455-456.
17. Amiott EA, Lott P, Soto J, Kang PB, McCaffery JM, et al. (2008) Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations. Exp Neurol 211: 115-127.
18. Guillet V, Gueguen N, Verny C, Ferre M, Homedan C, et al. (2010) Adenine nucleotide translocase is involved in a mitochondrial coupling defect in MFN2-related Charcot-Marie-Tooth type 2A disease. Neurogenetics 11: 127-133.
19. Kryukov GV, Pennacchio LA, Sunyaev SR, (2007) Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am J Hum Genet 80: 727-739.
20. Huang P, Galloway CA, Yoon Y, (2011) Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins. PLos One 6: e20655.
21. Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, et al. (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci USA 105: 1638-1643.
22. Yarosh W, Monserrate J, Tong JJ, Tse S, Le PK, et al. (2008) The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. PLoS Genet 4: e6.
23. Dorn GW 2nd, Clark CF, Eschenbacher WH, Kang MY, Engelhard JT, et al (2011) MARF and Opa1 control mitochondrial and cardiac function in Drosophila. Circ Res 108: 12-17.
24. Kijima K, Numakura C, Izumino H, Umetsu K, Nezu A, et al. (2005) Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A. Hum Genet 116: 23-27.
25. Engelfried K, Vorgerd M, Hagedorn M, Haas G, Gilles J, et al. (2006) Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2). BMC Med Genet 7: 53.
26. Casasnovas C, Banchs I, Cassereau J, Gueguen N, Chevrollier A, et al. (2010) Phenotypic spectrum of MFN2 mutations in the Spanish population. J Med Genet 47: 249-256.
27. McCorquodale DS 3rd, Montenegro G, Peguero A, Carlson N, Speziani F, et al (2011) Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2. J Neurol 258: 1234-1239.
28. Kumar P, Henikoff S, Ng PC, (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4: 1073-1081.
29. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, et al. (2010) A method and server for predicting damaging missense mutations. Nat Methods 7: 248-249.
30. Liu X, Jian X, Boerwinkle E, (2011) dbNSFP: a lightweight database of human nonsynonymous SNPs and their functional predictions. Hum Mutat 32: 894-899.
31. Santel A, Fuller MT, (2001) Control of mitochondrial morphology by a human mitofusin. J Cell Sci 114: 867-874.
32. Richardson EC, Pichaud F, (2010) Crumbs is required to achieve proper organ size control during Drosophila head development. Development 137: 641-650.
33. Sandu C, Ryoo HD, Steller H, (2010) Drosophila IAP antagonists form multimeric complexes to promote cell death. J Cell Biol 190: 1039-1052.
34. Caldeira J, Simoes-Correia J, Paredes J, Pinto MT, Sousa S, et al. (2011) CPEB1, a novel gene silenced in gastric cancer: a Drosophila approach. Gut.
35. Yun J, Cao JH, Dodson MW, Clark IE, Kapahi P, et al. (2008) Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component of the PINK1/PARKIN pathway in vivo. J Neurosci 28: 14500-14510.
36. Deng H, Dodson MW, Huang H, Guo M, (2008) The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci USA 105: 14503-14508.
37. Lo PC, Frasch M, (2001) A role for the COUP-TF-related gene seven-up in the diversification of cardioblast identities in the dorsal vessel of Drosophila. Mech Dev 104: 49-60.
38. Piazza N, Gosangi B, Devilla S, Arking R, Wessells R, (2009) Exercise-training in young Drosophila melanogaster reduces age-related decline in mobility and cardiac performance. PLos One 4: e5886.
39. Goldstein JA, Kelly SM, LoPresti PP, Heydemann A, Earley JU, et al. (2011) SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy. Hum Mol Genet 20: 894-904.
40. Chan DC, (2006) Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22: 79-99.
41. Exome Variant Server, NHLBI Exome Sequencing Project (ESP) Seattle, WA. pp. Available: http://evs.gs.washington.edu/EVS/. Accessed 2012 Feb.
42. Choma MA, Izatt SD, Wessells RJ, Bodmer R, Izatt JA, (2006) Images in cardiovascular medicine: in vivo imaging of the adult Drosophila melanogaster heart with real-time optical coherence tomography. Circulation 114: e35-36.
43. Allikian MJ, Bhabha G, Dospoy P, Heydemann A, Ryder P, et al. (2007) Reduced life span with heart and muscle dysfunction in Drosophila sarcoglycan mutants. Hum Mol Genet 16: 2933-2943.