The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells.
Journal:
Mol. Biol. Cell 2011 JulAuthors:
Zhang Z, Wakabayashi N, Wakabayashi J, Tamura Y, Song WJ, Sereda S, Clerc P, Polster BM, Aja SM, Pletnikov MV, Kensler TW, Shirihai OS, Iijima M, Hussain MA, Sesaki H
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 maintai
...[more]ned 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.[less]
Mesh Headings:
Adenosine Triphosphate, Animals, Apoptosis, Cell Proliferation, DNA, Mitochondrial, Dynamins, Electron Transport Complex IV, GTP Phosphohydrolases, Glucose, Glucose Intolerance, Hyperglycemia, Insulin, Insulin-Secreting Cells, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Receptor-Interacting Protein Serine-Threonine Kinases