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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/H359    most recent 00467.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Dabkowski, E. R. Articles by Hollander, J. M. Search for Related Content PubMed PubMed Citation Articles by Dabkowski, E. R. Articles by Hollander, J. M.

Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations

¹Division of Exercise Physiology, Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, and ²Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown; and ³Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia

Submitted 5 May 2008 ; accepted in final form 2 December 2008

Diabetic cardiomyopathy is the leading cause of heart failure among diabetic patients, and mitochondrial dysfunction has been implicated as an underlying cause in the pathogenesis. Cardiac mitochondria consist of two spatially, functionally, and morphologically distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). SSM are situated beneath the plasma membrane, whereas IFM are embedded between myofibrils. The goal of this study was to determine whether spatially distinct cardiac mitochondrial subpopulations respond differently to a diabetic phenotype. Swiss-Webster mice were subjected to intraperitoneal injections of streptozotocin or citrate saline vehicle. Five weeks after injections, diabetic hearts displayed decreased rates of contraction, relaxation, and left ventricular developed pressures (P < 0.05 for all three). Both mitochondrial size (forward scatter, P < 0.01) and complexity (side scatter, P < 0.01) were decreased in diabetic IFM but not diabetic SSM. Electron transport chain complex II respiration was decreased in diabetic SSM (P < 0.05) and diabetic IFM (P < 0.01), with the decrease being greater in IFM. Furthermore, IFM complex I respiration and complex III activity were decreased with diabetes (P < 0.01) but were unchanged in SSM. Superoxide production was increased only in diabetic IFM (P < 0.01). Oxidative damage to proteins and lipids, indexed through nitrotyrosine residues and lipid peroxidation, were higher in diabetic IFM (P < 0.05 and P < 0.01, respectively). The mitochondria-specific phospholipid cardiolipin was decreased in diabetic IFM (P < 0.01) but not SSM. These results indicate that diabetes mellitus imposes a greater stress on the IFM subpopulation, which is associated, in part, with increased superoxide generation and oxidative damage, resulting in morphological and functional abnormalities that may contribute to the pathogenesis of diabetic cardiomyopathy.

diabetes; free radical; mitochondria

This article has been cited by other articles:

				M. Schwarzer and T. Doenst Letter to the editor: "Does a reduction in ADP-limited respiration indicate impaired mitochondrial function?" Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H889 - H889. [Full Text] [PDF]

				E. R. Dabkowski and J. M. Hollander Reply to "Letter to the editor: 'Does a reduction in ADP-limited respiration indicate impaired mitochondrial function?'" Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H890 - H890. [Full Text] [PDF]