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Cardiac ischemia reperfusion elicits increased mitochondrial mass but decreased mitochondrial respiration in mice
Author(s) -
Kalogeris Theodore John,
Wang Meifang,
Korthuis Ronald J.
Publication year - 2013
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.27.1_supplement.682.7
Subject(s) - mitochondrial biogenesis , mitochondrial dna , mitochondrion , ischemia , respiration , respiratory system , medicine , biology , endocrinology , gene , microbiology and biotechnology , anatomy , biochemistry
Modulation of mitochondrial biogenesis (MB) has been proposed to play a potentially critical role in the cardiac response to ischemia‐reperfusion (I/R), however, the specific effect of IR on MB has been little studied. We previously observed a significant increase in apparent cardiac mitochondrial mass after I/R in mice. Here we examined whether I/R‐induced increases in mitochondrial mass were associated with changes in mitochondrial respiratory activity. Mice were subjected to 30 occlusion of the left anterior descending coronary artery followed by 4 h reperfusion. Hearts were harvested for determination of both mitochondrial and nuclear DNA (mtDNA, nDNA, respectively) and measurement of respiratory activity in isolated mitochondria. The ratio of mtDNA/nDNA was increased 2–4‐fold by I/R. This was associated with significant decreases in both glutamate/malate‐ and succinate‐fueled oxygen consumption , as well as decreased respiratory control ratio (state3/state4). These results suggest that acute increases in mitochondrial biogenesis may be a compensatory but maladaptive response to I/R‐induced mitochondrial dysfunction, analogous to chronic mitochondrial cardiomyopathies. Supported by NIH AA‐014945 and HL‐095486.