title: Cardiac mitochondrial proteome dynamics with heavy water reveals stable rate of mitochondrial protein synthesis in heart failure despite decline in mitochondrial oxidative capacity.
abstract: 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.
authors.affiliation: Division of Cardiology and Department of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Kadambari Chandra
authors.initials: KC
authors.lastname: Shekar
authors.affiliation: Proteomics Core, Department of Research Core Services, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Division of Cardiology and Department of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Erinne R
authors.initials: ER
authors.lastname: Dabkowski
authors.affiliation: Division of Cardiology and Department of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Xu
authors.affiliation: Division of Cardiology and Department of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Rogerio Faustino
authors.initials: RF
authors.lastname: Ribeiro
authors.affiliation: Division of Cardiology and Department of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hecker
authors.affiliation: Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA; Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Rovshan G
authors.initials: RG
authors.lastname: Sadygov
authors.affiliation: Proteomics Core, Department of Research Core Services, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.affiliation: Department of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, OH, USA. Electronic address: kasumot@ccf.org.
authors.forename: Takhar
authors.initials: T
authors.lastname: Kasumov
authors.affiliation: Division of Cardiology and Department of Medicine, University of Maryland, Baltimore, MD, USA; Discipline of Physiology, University of Sydney, Anderson Stuart Building (F13) Sydney, NSW 2006 Australia.
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D000818:Animals; D001835:Body Weight; D019069:Cell Respiration; D002950:Citrate (si)-Synthase / Q000378:metabolism; D017666:Deuterium Oxide / Q000378:metabolism*; D006207:Half-Life; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009929:Organ Size; D010084:Oxidation-Reduction; D011312:Pressure; D014176:Protein Biosynthesis; D055550:Protein Stability; D020543:Proteome / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D020543:Proteome; D002950:Citrate (si)-Synthase; D017666:Deuterium Oxide
keywords: Cardiac failure; Deuterium; Mitochondria; Proteome dynamics