Cardiac mitochondrial proteome dynamics with heavy water reveals stable rate of mitochondrial protein synthesis in heart failure despite decline in mitochondrial oxidative capacity

Kadambari Chandra Shekar, Ling Li, Erinne R. Dabkowski, Wenhong Xu, Rogerio Faustino Ribeiro, Peter A. Hecker, Fabio A. Recchia, Rovshan G. Sadygov, Belinda Willard, Takhar Kasumov, William C. Stanley

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

We recently developed a method to measure mitochondrial proteome dynamics with heavy water (2H2O)-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.

Original languageEnglish (US)
Pages (from-to)88-97
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume75
DOIs
StatePublished - Oct 1 2014

Keywords

  • Cardiac failure
  • Deuterium
  • Mitochondria
  • Proteome dynamics

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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