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Distinct Mitochondrial Subpopulation Response in a Type 2 Diabetic Model
Author(s) -
Dabkowski Erinne R,
Williamson Courtney L,
Frisbee Jefferson C,
Brock Robert W,
Hollander John M
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.990.22
Subject(s) - mitochondrion , sarcolemma , medicine , endocrinology , bioenergetics , diabetic cardiomyopathy , myofibril , pathogenesis , type 2 diabetes , respiration , diabetes mellitus , biology , chemistry , myocyte , microbiology and biotechnology , anatomy , cardiomyopathy , heart failure
Mitochondrial dysfunction plays a critical role in the pathogenesis of type 2 diabetes mellitus. Examination of mitochondria is complicated by the fact that two spatially distinct mitochondria populations exist in the cardiac myocyte, interfibrillar mitochondria (IFM) which situate between the myofibrils, and subsarcolemmal mitochondria (SSM) which exist beneath the sarcolemma. The goal of this study was to determine whether spatially distinct cardiac mitochondrial subpopulations are differentially affected by type 2 diabetic insult. Db/db mice were sacrificed at 20 weeks of age and mitochondrial subpopulations isolated. State 3 respiration was significantly lower in db/db SSM contributing to decreased RCR ratios (P<0.05). Electron transport chain complex activities (I, III, IV) were significantly decreased only in diabetic SSM as compared to control (P<0.05 for all three). Uncoupling protein 3 was significantly increased only in db/db SSM (P<0.05). Manganese superoxide dismutase (MnSOD) protein was significantly elevated in db/db IFM suggesting a potential spatially‐specific protective mechanism. Mitochondrial heat shock protein 70 (mthsp70), a mitochondrial import protein, was significantly decreased only in db/db SSM. These findings suggest that type 2 diabetic insult impacts spatially distinct cardiac mitochondria differently with SSM displaying greater dysfunctional profiles.