The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells

被引：125

作者：

Zhang, Zhongyan ^{[1
]}

Wakabayashi, Nobunao ^{[2
]}

Wakabayashi, Junko ^{[1
]}

Tamura, Yasushi ^{[1
]}

Song, Woo-Jin ^{[3
,4
]}

Sereda, Sam ^{[5
]}

Clerc, Pascaline ^{[6
]}

Polster, Brian M. ^{[6
]}

Aja, Susan M. ^{[7
,8
]}

Pletnikov, Mikhail V. ^{[7
,9
]}

Kensler, Thomas W. ^{[2
]}

Shirihai, Orian S. ^{[5
]}

Iijima, Miho ^{[1
]}

Hussain, Mehboob A. ^{[3
,4
]}

Sesaki, Hiromi ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA

[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Pediat & Med, Div Metab, Baltimore, MD 21205 USA

[5] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[6] Univ Maryland, Sch Med, Trauma & Anesthesiol Res STAR Ctr, Dept Anesthesiol & Shock, Baltimore, MD 21201 USA

[7] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Sch Med, Ctr Metab & Obes Res, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

来源：

MOLECULAR BIOLOGY OF THE CELL | 2011年 / 22卷 / 13期

基金：

美国国家卫生研究院;

关键词：

DOMINANT OPTIC ATROPHY; MITOCHONDRIAL FUSION; INSULIN-SECRETION; OXIDATIVE STRESS; MEMBRANE FUSION; CYTOCHROME-C; MOUSE; DYSFUNCTION; METABOLISM; MORPHOLOGY;

D O I：

10.1091/mbc.E10-12-0933

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：2235 / 2245

页数：11

共 48 条

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