title: The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells.
abstract: Previous studies using in vitro cell culture systems have shown the role of the dynamin-related GTPase Opa1 in apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to be tested whether these functions of Opa1 are physiologically important in vivo in mammals. Here, using the Cre-loxP system, we deleted mouse Opa1 in pancreatic beta cells, in which glucose-stimulated ATP production in mitochondria plays a key role in insulin secretion. Beta cells lacking Opa1 maintained normal copy numbers of mtDNA; however, the amount and activity of electron transport chain complex IV were significantly decreased, leading to impaired glucose-stimulated ATP production and insulin secretion. In addition, in Opa1-null beta cells, cell proliferation was impaired, whereas apoptosis was not promoted. Consequently, mice lacking Opa1 in beta cells develop hyperglycemia. The data suggest that the function of Opa1 in the maintenance of the electron transport chain is physiologically relevant in beta cells.
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Nobunao
authors.initials: N
authors.lastname: Wakabayashi
authors.forename: Junko
authors.initials: J
authors.lastname: Wakabayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Woo-Jin
authors.initials: WJ
authors.lastname: Song
authors.forename: Sam
authors.initials: S
authors.lastname: Sereda
authors.forename: Pascaline
authors.initials: P
authors.lastname: Clerc
authors.forename: Brian M
authors.initials: BM
authors.lastname: Polster
authors.forename: Susan M
authors.initials: SM
authors.lastname: Aja
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.forename: Orian S
authors.initials: OS
authors.lastname: Shirihai
authors.forename: Miho
authors.initials: M
authors.lastname: Iijima
authors.forename: Mehboob A
authors.initials: MA
authors.lastname: Hussain
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D007328:Insulin; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse; D034281:Dynamins; D005947:Glucose