We recently developed a method to measure mitochondrial
proteome dynamics with
heavy water ((2)H2O)-based metabolic labeling and high resolution mass spectrometry. We reported the half-lives and synthesis rates of several
proteins in the two cardiac mitochondrial subpopulations, subsarcolemmal and interfibrillar (SSM and IFM), in Sprague Dawley rats. In the present study, we tested the hypothesis that the
mitochondrial protein synthesis rate is reduced in
heart failure, with possible differential changes in SSM versus IFM. Six to seven week old male Sprague Dawley rats underwent transverse aortic constriction (TAC) and developed moderate
heart failure after 22weeks.
Heart failure and
sham rats of the same age received
heavy water (5% in
drinking water) for up to 80days. Cardiac SSM and IFM were isolated from both groups and the
proteins were separated by 1D gel electrophoresis.
Heart failure reduced
protein content and increased the turnover rate of several
proteins involved in
fatty acid oxidation, electron transport chain and
ATP synthesis, while it decreased the turnover of other
proteins, including
pyruvate dehydrogenase subunit in IFM, but not in SSM. Because of these bidirectional changes, the average overall half-life of
proteins was not altered by
heart failure in both SSM and IFM. The kinetic measurements of individual
mitochondrial proteins presented in this study may contribute to a better understanding of the mechanisms responsible for mitochondrial alterations in the failing heart.