Phosphoproteome Analysis of Functional Mitochondria Isolated from Resting Human Muscle Reveals Extensive Phosphorylation of Inner Membrane Protein Complexes and Enzymes

Zhao, Xiaolu; León, Ileana R.; Bak, Steffen; Mogensen, Martin; Wrzesinski, Krzysztof; Højlund, Kurt; Jensen, Ole N.

doi:10.1074/mcp.m110.000299

Cited by 155 publications

(207 citation statements)

References 66 publications

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“…7). Recently, Zhao et al, combining different phosphopeptide enrichment approaches with high performance LC-MS/MS, presented the phosphorylation pattern of isolated mitochondria from muscle of five healthy volunteers [38]. The authors identified 155 distinct phosphorylation sites in 77 mitochondrial phosphoproteins.…”

Section: The Proteomic Profile Of Functional Mitochondriamentioning

confidence: 99%

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Diversity of human skeletal muscle in health and disease: Contribution of proteomics

Gelfi

Vasso

Cerretelli

2011

Journal of Proteomics

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Section: The Proteomic Profile Of Functional Mitochondriamentioning

confidence: 99%

“…Special emphasis shall also be placed on the study of human skeletal muscle mitochondria for the possible assessment of proteins from small samples of healthy and diseased skeletal muscles [37,38]. In the above investigation, 100 mg of tissue biopsies were utilized for mitochondrial enrichment.…”

Section: The Proteomic Profile Of Functional Mitochondriamentioning

confidence: 99%

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

Gelfi

Vasso

Cerretelli

2011

Journal of Proteomics

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“…Following translation, many different facets of protein function (activity, subcellular localization, protein-protein interactions) can be altered by the addition of functional groups to specific residues in the protein. The most well-described PTM is likely phosphorylation, and proteomics screens have revealed widespread phosphorylation of mitochondrial proteins [59]. The activity of specific mitochondrial proteins, such as uncoupling protein 3, has been shown to be directly regulated by phosphorylation [60].…”

Section: Intrinsic Factors Regulating Mitochondrial Functionmentioning

confidence: 99%

Mitochondrial Metabolism and Insulin Action

Turner¹

2013

Type 2 Diabetes

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“…The importance of PTM mole fraction is not as critical for signaling molecules, such as kinases, acetylases, deacetylases, phosphatases, or ion channels, where the modification of a few copies can influence numerous downstream events or the membrane potential. This requirement is often overlooked when using high-sensitivity methods for detecting phosphorylated proteins, including phosphopeptide enhancement mass spectrometry (MS) (24,58,121,165,236), radiolabeling (6,29,128), and high-sensitivity MS (156,175), all of which permit the detection of a few copies of phosphorylated peptides in the enzyme protein pool. Another line of evidence for the regulatory role of a protein phosphorylation site may include changes in enzyme activity upon specific amino acid substitution that simulate or eliminate the PTM (1,101,159).…”

Section: Introductionmentioning

confidence: 99%

Cardiac mitochondrial matrix and respiratory complex protein phosphorylation

Covián

Balaban

2012

American Journal of Physiology-Heart and Circulatory Physiology

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Covian R, Balaban RS. Cardiac mitochondrial matrix and respiratory complex protein phosphorylation. Am J Physiol Heart Circ Physiol 303: H940 -H966, 2012. First published August 10, 2012; doi:10.1152/ajpheart.00077.2012.-It has become appreciated over the last several years that protein phosphorylation within the cardiac mitochondrial matrix and respiratory complexes is extensive. Given the importance of oxidative phosphorylation and the balance of energy metabolism in the heart, the potential regulatory effect of these classical signaling events on mitochondrial function is of interest. However, the functional impact of protein phosphorylation and the kinase/phosphatase system responsible for it are relatively unknown. Exceptions include the well-characterized pyruvate dehydrogenase and branched chain ␣-ketoacid dehydrogenase regulatory system. The first task of this review is to update the current status of protein phosphorylation detection primarily in the matrix and evaluate evidence linking these events with enzymatic function or protein processing. To manage the scope of this effort, we have focused on the pathways involved in energy metabolism. The high sensitivity of modern methods of detecting protein phosphorylation and the low specificity of many kinases suggests that detection of protein phosphorylation sites without information on the mole fraction of phosphorylation is difficult to interpret, especially in metabolic enzymes, and is likely irrelevant to function. However, several systems including protein translocation, adenine nucleotide translocase, cytochrome c, and complex IV protein phosphorylation have been well correlated with enzymatic function along with the classical dehydrogenase systems. The second task is to review the current understanding of the kinase/phosphatase system within the matrix. Though it is clear that protein phosphorylation occurs within the matrix, based on 32 P incorporation and quantitative mass spectrometry measures, the kinase/phosphatase system responsible for this process is ill-defined. An argument is presented that remnants of the much more labile bacterial protein phosphoryl transfer system may be present in the matrix and that the evaluation of this possibility will require the application of approaches developed for bacterial cell signaling to the mitochondria.kinase; phosphatase; citric acid cycle; oxidative phosphorylation; protein transport; mitochondria intermembrane space; phosphohistidine; adenine nucleotide translocase; pyruvate dehydrogenase; branched chain ␣-ketoacid dehydrogenase THIS REVIEW ARTICLE is part of a collection on Post-translational Protein Modification in Metabolic Stress. Other articles appearing in this collection, as well as a full archive of all Review collections, can be found online at http://ajpheart. physiology.org/.

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Phosphoproteome Analysis of Functional Mitochondria Isolated from Resting Human Muscle Reveals Extensive Phosphorylation of Inner Membrane Protein Complexes and Enzymes

Cited by 155 publications

References 66 publications

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

Mitochondrial Metabolism and Insulin Action

Cardiac mitochondrial matrix and respiratory complex protein phosphorylation

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