title: Polymorphism, heteroplasmy, mitochondrial fusion and diabetes.
abstract: Mitochondrial DNA (mtDNA) is highly susceptible to mutations that result in polymorphisms and diseases including diabetes. We analyzed heteroplasmy, polymorphisms related to diabetes, and complementation by fusogenic proteins. Cytoplast fusion and microinjection allow, defects in mutated mtDNA inside a heteroplasmic cell to be complemented by fusing two mitochondria via human fusogenic proteins. We characterized three hfzos as well as two OPAls that prevent apoptosis. Two coiled coil domains and GTPase domains in these fusogenic proteins regulate membrane fusion. The hfzo genes were expressed mainly in the brain and in muscle that are postmitotic, but not in the pancreas. Under the influence of polymorphisms of mtDNA and nDNA, the vicious circle of reactive oxygen species and mutations in cell can be alleviated by mitochondrial fusion.
authors.affiliation: High Technology Research Center, Kagawa Nutrition University, Chiyoda Sakado, Saitama 350-0288, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Sato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umetsu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sone
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Azusa
authors.initials: A
authors.lastname: Saigusa
authors.forename: Sayuri
authors.initials: S
authors.lastname: Aita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kagawa
mesh_terms: D000818:Animals; D001208:Asia; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D015870:Gene Expression; D015316:Genetic Therapy; D006239:Haplotypes; D006801:Humans; D008561:Membrane Fusion; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species