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World J Cardiol. May 26, 2012; 4(5): 148-156
Published online May 26, 2012. doi: 10.4330/wjc.v4.i5.148
Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes
Dimitry A Chistiakov, Igor A Sobenin, Yuri V Bobryshev, Alexander N Orekhov
Dimitry A Chistiakov, Igor A Sobenin, Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, 117997 Moscow, Russia
Dimitry A Chistiakov, Yuri V Bobryshev, Alexander N Orekhov, Institute for Atherosclerosis Research, Skolkovo Innovative Centre, 121609 Moscow, Russia
Igor A Sobenin, Alexander N Orekhov, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, 125315 Moscow, Russia
Igor A Sobenin, Russian Cardiology Research and Production Complex, 121552 Moscow, Russia
Yuri V Bobryshev, Faculty of Medicine, School of Medical Sciences, University of New South Wales, NSW 2052, Sydney, Australia
Author contributions: All authors participated in conception of the topic, literature search and analysis, writing of the manuscript, and approved the final version of the manuscript.
Supported by The Russian Ministry of Science and Education
Correspondence to: Yuri V Bobryshev, PhD, Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, NSW 2052, Sydney, Australia. y.bobryshev@unsw.edu.au
Telephone: +61-2-93851217 Fax: +61-2-93851217
Received: March 22, 2012
Revised: April 30, 2012
Accepted: May 7, 2012
Published online: May 26, 2012
Abstract

Mitochondrial DNA (mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system. This explains an increased mutation rate of mtDNA that results in heteroplasmy, e.g., the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion. In diabetes mellitus, glycotoxicity, advanced oxidative stress, collagen cross-linking, and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction, which in turn further contributes to the oxidative damage of the diabetic vascular wall, endothelial dysfunction, and atherosclerosis.

Keywords: Mitochondrial DNA; Mutation; Heteroplasmy; Atherosclerosis; Diabetes; Oxidative stress; Ultrastructure