The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells-Reference-Cited by-同舟云学术

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

Published:2011-07 Issue:13 Volume:22 Page:2235-2245
ISSN:1059-1524
Container-title:Molecular Biology of the Cell
language:en
Short-container-title:MBoC

Author:

Zhang Zhongyan¹,Wakabayashi Nobunao²,Wakabayashi Junko¹,Tamura Yasushi¹,Song Woo-Jin³,Sereda Sam⁴,Clerc Pascaline⁵,Polster Brian M.⁵,Aja Susan M.⁶,Pletnikov Mikhail V.⁷,Kensler Thomas W.²,Shirihai Orian S.⁴,Iijima Miho¹,Hussain Mehboob A.³,Sesaki Hiromi¹

Affiliation:

1. Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

2. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205

3. Department of Biological Chemistry and Department of Pediatrics and Medicine, Metabolism Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205

4. Department of Medicine, Boston University School of Medicine, Boston, MA 02118

5. Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD 21201

6. Department of Neurosciences and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205

7. Department of Psychiatry and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205

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.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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