Mitochondria mediated cell death in diabetes.
Mitochondrial dysfunction plays a role in the pathogenesis of a wide range of diseases that involve disordered cellular fuel metabolism and survival/death pathways, including neurodegenerative diseases, cancer and diabetes. Cytokine, virus recognition and cellular stress pathways converging on mitochondria cause apoptotic and/or necrotic cell death of beta-cells in type-1 diabetes. Moreover, since mitochondria generate crucial metabolic signals for glucose stimulated insulin secretion (GSIS), mitochondrial dysfunction underlies both the functional derangement of GSIS and (over-nutrition) stress-induced apoptotic/necrotic beta-cell death, hallmarks of type-2 diabetes. The apparently distinct mechanisms governing beta-cell life/death decisions during the development of diabetes provide a remarkable example where remote metabolic, immune and stress signalling meet with mitochondria mediated apoptotic/necrotic death pathways to determine the fate of the beta-cell. We summarize the main findings supporting such a pivotal role of mitochondria in beta-cell death in the context of current trends in diabetes research.
Szabadkai
Gyorgy
G
Department of Cell and Developmental Biology, Mitochondrial Biology Group, University College London, Gower Street, WC1E 6BT London, UK. g.szabadkai@ucl.ac.uk
Duchen
Michael R
MR
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism*