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Experimental Diabetes Research
Volume 2012, Article ID 642038, 16 pages
Review Article

Mitochondrial Dysregulation in the Pathogenesis of Diabetes: Potential for Mitochondrial Biogenesis-Mediated Interventions

1Department of Biology, York University, Toronto, ON, Canada M3J 1P3
2Muscle Health Research Center (MHRC), York University, Toronto, ON, Canada M3J 1P3
3Division of Kinesiology, Laval University, Québec City, QC, Canada G1K 7P4
4Department of Cardiac Surgery, Laval University, Québec City, QC, Canada G1V 4G5
5School of Kinesiology and Health Science, York University, Room 302, Farquharson Life Sciences Building, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3

Received 7 June 2011; Accepted 8 September 2011

Academic Editor: Robert A. Harris

Copyright © 2012 Anna-Maria Joseph et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions.