TY - JOUR
T1 - The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells
AU - Zhang, Zhongyan
AU - Wakabayashi, Nobunao
AU - Wakabayashi, Junko
AU - Tamura, Yasushi
AU - Song, Woo Jin
AU - Sereda, Sam
AU - Clerc, Pascaline
AU - Polster, Brian M.
AU - Aja, Susan M.
AU - Pletnikov, Mikhail V.
AU - Kensler, Thomas W.
AU - Shirihai, Orian S.
AU - Iijima, Miho
AU - Hussain, Mehboob A.
AU - Sesaki, Hiromi
PY - 2011/7/1
Y1 - 2011/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79959910616&partnerID=8YFLogxK
U2 - 10.1091/mbc.E10-12-0933
DO - 10.1091/mbc.E10-12-0933
M3 - Article
AN - SCOPUS:79959910616
SN - 1059-1524
VL - 22
SP - 2235
EP - 2245
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 13
ER -
