Spatial and temporal dynamics of the cardiac mitochondrial proteome
EXPERT REVIEW OF PROTEOMICS
2015; 12 (2): 133-146
Mitochondrial protein turnover: Methods to measure turnover rates on a large scale
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2015; 78: 54-61
Mitochondrial proteins alter in their composition and quantity drastically through time and space in correspondence to changing energy demands and cellular signaling events. The integrity and permutations of this dynamism are increasingly recognized to impact the functions of the cardiac proteome in health and disease. This article provides an overview on recent advances in defining the spatial and temporal dynamics of mitochondrial proteins in the heart. Proteomics techniques to characterize dynamics on a proteome scale are reviewed and the physiological consequences of altered mitochondrial protein dynamics are discussed. Lastly, we offer our perspectives on the unmet challenges in translating mitochondrial dynamics markers into the clinic.
View details for DOI 10.1586/14789450.2015.1024227
View details for Web of Science ID 000351771000004
View details for PubMedID 25752359
View details for PubMedCentralID PMC4721584
Molecular- and Organelle-Based Predictive Paradigm Underlying Recovery by Left Ventricular Assist Device Support
2014; 7 (2): 359-366
Characterization, Design, and Function of the Mitochondrial Proteome: From Organs to Organisms
JOURNAL OF PROTEOME RESEARCH
2014; 13 (2): 433-446
Mitochondrial proteins carry out diverse cellular functions including ATP synthesis, ion homeostasis, cell death signaling, and fatty acid metabolism and biogenesis. Compromised mitochondrial quality control is implicated in various human disorders including cardiac diseases. Recently it has emerged that mitochondrial protein turnover can serve as an informative cellular parameter to characterize mitochondrial quality and uncover disease mechanisms. The turnover rate of a mitochondrial protein reflects its homeostasis and dynamics under the quality control systems acting on mitochondria at a particular cell state. This review article summarizes some recent advances and outstanding challenges for measuring the turnover rates of mitochondrial proteins in health and disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".
View details for DOI 10.1016/j.yjmcc.2014.10.012
View details for Web of Science ID 000348484400007
View details for PubMedID 25451168
View details for PubMedCentralID PMC4746024
Metabolic Labeling Reveals Proteome Dynamics of Mouse Mitochondria
MOLECULAR & CELLULAR PROTEOMICS
2012; 11 (12): 1586-1594
Mitochondria are a common energy source for organs and organisms; their diverse functions are specialized according to the unique phenotypes of their hosting environment. Perturbation of mitochondrial homeostasis accompanies significant pathological phenotypes. However, the connections between mitochondrial proteome properties and function remain to be experimentally established on a systematic level. This uncertainty impedes the contextualization and translation of proteomic data to the molecular derivations of mitochondrial diseases. We present a collection of mitochondrial features and functions from four model systems, including two cardiac mitochondrial proteomes from distinct genomes (human and mouse), two unique organ mitochondrial proteomes from identical genetic codons (mouse heart and mouse liver), as well as a relevant metazoan out-group (drosophila). The data, composed of mitochondrial protein abundance and their biochemical activities, capture the core functionalities of these mitochondria. This investigation allowed us to redefine the core mitochondrial proteome from organs and organisms, as well as the relevant contributions from genetic information and hosting milieu. Our study has identified significant enrichment of disease-associated genes and their products. Furthermore, correlational analyses suggest that mitochondrial proteome design is primarily driven by cellular environment. Taken together, these results connect proteome feature with mitochondrial function, providing a prospective resource for mitochondrial pathophysiology and developing novel therapeutic targets in medicine.
View details for DOI 10.1021/pr400539j
View details for Web of Science ID 000331164100010
View details for PubMedID 24070373
View details for PubMedCentralID PMC4076470
Perspectives on: SGP symposium on mitochondrial physiology and medicine: mitochondrial proteome design: from molecular identity to pathophysiological regulation.
journal of general physiology
2012; 139 (6): 395-406
Mitochondrial dysfunction is associated with many human diseases. Mitochondrial damage is exacerbated by inadequate protein quality control and often further contributes to pathogenesis. The maintenance of mitochondrial functions requires a delicate balance of continuous protein synthesis and degradation, i.e. protein turnover. To understand mitochondrial protein dynamics in vivo, we designed a metabolic heavy water ((2)H(2)O) labeling strategy customized to examine individual protein turnover in the mitochondria in a systematic fashion. Mice were fed with (2)H(2)O at a minimal level (<5% body water) without physiological impacts. Mitochondrial proteins were analyzed from 9 mice at each of the 13 time points between 0 and 90 days (d) of labeling. A novel multiparameter fitting approach computationally determined the normalized peak areas of peptide mass isotopomers at initial and steady-state time points and permitted the protein half-life to be determined without plateau-level (2)H incorporation. We characterized the turnover rates of 458 proteins in mouse cardiac and hepatic mitochondria and found median turnover rates of 0.0402 d(-1) and 0.163 d(-1), respectively, corresponding to median half-lives of 17.2 d and 4.26 d. Mitochondria in the heart and those in the liver exhibited distinct turnover kinetics, with limited synchronization within functional clusters. We observed considerable interprotein differences in turnover rates in both organs, with half-lives spanning from hours to months (? 60 d). Our proteomics platform demonstrates the first large-scale analysis of mitochondrial protein turnover rates in vivo, with potential applications in translational research.
View details for DOI 10.1074/mcp.M112.021162
View details for Web of Science ID 000313557000007
View details for PubMedID 22915825
View details for PubMedCentralID PMC3518123