Post-Translational Modifications of Cardiac Mitochondrial Proteins in Cardiovascular Disease: Not Lost in Translation

Protein post-translational modifications (PTMs) are crucial in regulating cellular biology by playing key roles in processes such as the rapid on and off switching of signaling network and the regulation of enzymatic activities without affecting gene expressions. PTMs lead to conformational changes in the tertiary structure of protein and resultant regulation of protein function such as activation, inhibition, or signaling roles. PTMs such as phosphorylation, acetylation, and S-nitrosylation of specific sites in proteins have key roles in regulation of mitochondrial functions, thereby contributing to the progression to heart failure. Despite the extensive study of PTMs in mitochondrial proteins much remains unclear. Further research is yet to be undertaken to elucidate how changes in the proteins may lead to cardiovascular and metabolic disease progression in particular. We aimed to summarize the various types of PTMs that occur in mitochondrial proteins, which might be associated with heart failure. This study will increase the understanding of cardiovascular diseases through PTM.

[1]  Hidde Ploegh,et al.  Chemical biology: Dressed-up proteins , 2007, Nature.

[2]  H. E. Marshall,et al.  Protein S-nitrosylation: purview and parameters , 2005, Nature Reviews Molecular Cell Biology.

[3]  Colin Simpson,et al.  Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003: A Population Study of 5.1 Million People , 2009, Circulation.

[4]  T. Wenz,et al.  Post-translational modification of mitochondria as a novel mode of regulation , 2014, Experimental Gerontology.

[5]  G. Hart,et al.  Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. , 2011, Annual review of biochemistry.

[6]  Devin K Schweppe,et al.  Quantitative Phosphoproteomics Identifies Substrates and Functional Modules of Aurora and Polo-Like Kinase Activities in Mitotic Cells , 2011, Science Signaling.

[7]  N. Grishin,et al.  Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. , 2006, Molecular cell.

[8]  M. Holness,et al.  Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. , 2003, American journal of physiology. Endocrinology and metabolism.

[9]  M. Larsen,et al.  The phosphorylation pattern of bovine heart complex I subunits , 2007, Proteomics.

[10]  Norman Fleischer,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. , 1993 .

[11]  Yixue Li,et al.  Regulation of Cellular Metabolism by Protein Lysine Acetylation , 2010, Science.

[12]  J. Zweier,et al.  Mitochondrial Complex II in the Post-ischemic Heart , 2007, Journal of Biological Chemistry.

[13]  E. Tajkhorshid,et al.  Tyrosine phosphorylation by Src within the cavity of the adenine nucleotide translocase 1 regulates ADP/ATP exchange in mitochondria. , 2010, American journal of physiology. Cell physiology.

[14]  E. R. Taylor,et al.  Interactions of mitochondrial thiols with nitric oxide. , 2003, Antioxidants & redox signaling.

[15]  D. Kelly,et al.  Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. , 1996, Circulation.

[16]  C. Hoppel,et al.  Cardiac mitochondria in heart failure: normal cardiolipin profile and increased threonine phosphorylation of complex IV. , 2011, Biochimica et biophysica acta.

[17]  B. O’Malley,et al.  Nuclear receptor coregulators: judges, juries, and executioners of cellular regulation. , 2007, Molecular cell.

[18]  Wayne F. Patton,et al.  Analysis of Steady-state Protein Phosphorylation in Mitochondria Using a Novel Fluorescent Phosphosensor Dye* , 2003, Journal of Biological Chemistry.

[19]  Ileana M. Cristea,et al.  Sirtuin 4 Is a Lipoamidase Regulating Pyruvate Dehydrogenase Complex Activity , 2014, Cell.

[20]  E. Koc,et al.  Regulation of mammalian mitochondrial translation by post-translational modifications. , 2012, Biochimica et biophysica acta.

[21]  G. R. Wagner,et al.  Mitochondrial Acetylation and Diseases of Aging , 2011, Journal of aging research.

[22]  C. Brenner,et al.  The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. , 2003, Current medicinal chemistry.

[23]  Wanqing Sun,et al.  The role of Pyruvate Dehydrogenase Complex in cardiovascular diseases. , 2015, Life sciences.

[24]  Robert A. Harris,et al.  PyTMs: a useful PyMOL plugin for modeling common post-translational modifications , 2014, BMC Bioinformatics.

[25]  Sangkyu Lee Post-Translational Modification of Proteins in Toxicological Research: Focus on Lysine Acylation , 2013, Toxicological research.

[26]  K. M. Popov,et al.  Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. , 1998, The Biochemical journal.

[27]  Chunxiang Zheng,et al.  Protein Interactions, Post-translational Modifications and Topologies in Human Cells* , 2013, Molecular & Cellular Proteomics.

[28]  J. Dixon,et al.  Mitochondrial modulation: reversible phosphorylation takes center stage? , 2006, Trends in biochemical sciences.

[29]  R. Cole,et al.  Removal of Abnormal Myofilament O-GlcNAcylation Restores Ca2+ Sensitivity in Diabetic Cardiac Muscle , 2015, Diabetes.

[30]  S. Srinivasan,et al.  Protein Kinase A-mediated Phosphorylation Modulates Cytochrome c Oxidase Function and Augments Hypoxia and Myocardial Ischemia-related Injury* , 2006, Journal of Biological Chemistry.

[31]  J. Stock,et al.  Histidine protein kinases: key signal transducers outside the animal kingdom , 2002, Genome Biology.

[32]  Zhihong Zhang,et al.  Identification of lysine succinylation as a new post-translational modification. , 2011, Nature chemical biology.

[33]  M. Gheorghiade,et al.  Mitochondria as a therapeutic target in heart failure. , 2013, Journal of the American College of Cardiology.

[34]  Edward L. Huttlin,et al.  A Tissue-Specific Atlas of Mouse Protein Phosphorylation and Expression , 2010, Cell.

[35]  Melanie Y. White,et al.  Mitochondria: A mirror into cellular dysfunction in heart disease , 2008, Proteomics. Clinical applications.

[36]  Alexander M. Wolf,et al.  Caloric Restriction Primes Mitochondria for Ischemic Stress by Deacetylating Specific Mitochondrial Proteins of the Electron Transport Chain , 2011, Circulation research.

[37]  R. Ionescu,et al.  Separation of post-translational modifications in monoclonal antibodies by exploiting subtle conformational changes under mildly acidic conditions. , 2010, Journal of chromatography. A.

[38]  J. Yates,et al.  A method for the comprehensive proteomic analysis of membrane proteins , 2003, Nature Biotechnology.

[39]  Marjan Gucek,et al.  The NAD-dependent deacetylase SIRT2 is required for programmed necrosis , 2012, Nature.

[40]  Ole Nørregaard Jensen,et al.  Phosphoproteome Analysis of Functional Mitochondria Isolated from Resting Human Muscle Reveals Extensive Phosphorylation of Inner Membrane Protein Complexes and Enzymes* , 2010, Molecular & Cellular Proteomics.

[41]  B. O’Rourke,et al.  Metabolism leaves its mark on the powerhouse: recent progress in post-translational modifications of lysine in mitochondria , 2014, Front. Physiol..

[42]  Mitchell W. Krucoff,et al.  Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, th , 2001, Journal of the American College of Cardiology.

[43]  E. Block,et al.  Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells. , 2005, American journal of physiology. Cell physiology.

[44]  Eric Verdin,et al.  Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2 , 2006, Proceedings of the National Academy of Sciences.

[45]  B. Robinson,et al.  Control of oxygen free radical formation from mitochondrial complex I: roles for protein kinase A and pyruvate dehydrogenase kinase. , 2002, Free radical biology & medicine.

[46]  C. Steegborn,et al.  Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. , 2008, Journal of molecular biology.

[47]  G. Booz,et al.  Focus on mitochondria dysfunction and dysregulation in heart failure: towards new therapeutic strategies to improve heart function. , 2011, Congestive heart failure.

[48]  K. M. Popov,et al.  Primary structure of pyruvate dehydrogenase kinase establishes a new family of eukaryotic protein kinases. , 1993, The Journal of biological chemistry.

[49]  T. Roche,et al.  Marked Differences between Two Isoforms of Human Pyruvate Dehydrogenase Kinase* , 2000, The Journal of Biological Chemistry.

[50]  F. Sánchez‐Madrid,et al.  Post-Translational Modifications of Exosomal Proteins , 2014, Front. Immunol..

[51]  P. Kennelly,et al.  Fancy meeting you here! A fresh look at "prokaryotic" protein phosphorylation , 1996, Journal of bacteriology.

[52]  R. Apweiler,et al.  Phosphoproteome Analysis Reveals Regulatory Sites in Major Pathways of Cardiac Mitochondria* , 2010, Molecular & Cellular Proteomics.

[53]  S. Strumiło Short-term regulation of the mammalian pyruvate dehydrogenase complex. , 2005, Acta biochimica Polonica.

[54]  Kong-Joo Lee,et al.  Post-translational modifications and their biological functions: proteomic analysis and systematic approaches. , 2004, Journal of biochemistry and molecular biology.

[55]  E. Braunwald,et al.  A tale of coronary artery disease and myocardial infarction. , 2012, The New England journal of medicine.

[56]  Robert V Farese,et al.  SIRT 3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation , 2010 .

[57]  Edwin Smith,et al.  The Language of Histone Crosstalk , 2010, Cell.

[58]  N. Sundaresan,et al.  SIRT3 Is a Stress-Responsive Deacetylase in Cardiomyocytes That Protects Cells from Stress-Mediated Cell Death by Deacetylation of Ku70 , 2008, Molecular and Cellular Biology.

[59]  Eric Verdin,et al.  Mammalian Sir2 Homolog SIRT3 Regulates Global Mitochondrial Lysine Acetylation , 2007, Molecular and Cellular Biology.

[60]  Gene Kim,et al.  Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. , 2009, The Journal of clinical investigation.

[61]  M. Obayashi,et al.  Mechanism of activation of branched-chain alpha-keto acid dehydrogenase complex by exercise. , 2001, Biochemical and biophysical research communications.

[62]  Hua Cai,et al.  Mitochondrial proteome design: From molecular identity to pathophysiological regulation , 2012, The Journal of general physiology.

[63]  G. Hart,et al.  O-linked beta-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress. , 2010, Biochimica et biophysica acta.

[64]  T. Finkel,et al.  Mitochondrial metabolism, sirtuins, and aging. , 2012, Cold Spring Harbor perspectives in biology.

[65]  S. Javadov,et al.  Mitochondrial Permeability Transition Pore Opening as a Promising Therapeutic Target in Cardiac Diseases , 2009, Journal of Pharmacology and Experimental Therapeutics.

[66]  K. Ito,et al.  Impact of post-translational modifications of proteins on the inflammatory process. , 2007, Biochemical Society transactions.

[67]  Derek J. Bailey,et al.  A quantitative map of the liver mitochondrial phosphoproteome reveals posttranslational control of ketogenesis. , 2012, Cell metabolism.

[68]  R. Danziger,et al.  Non-histone lysine acetylated proteins in heart failure. , 2012, Biochimica et biophysica acta.

[69]  I. Fearnley,et al.  The Phosphorylation of Subunits of Complex I from Bovine Heart Mitochondria* , 2004, Journal of Biological Chemistry.

[70]  P. Thompson,et al.  Chemical and biological methods to detect post‐translational modifications of arginine , 2014, Biopolymers.

[71]  Yong Chen,et al.  Cyclophilin D Modulates Mitochondrial Acetylome , 2013, Circulation research.

[72]  Aase Handberg,et al.  Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes* , 2003, The Journal of Biological Chemistry.

[73]  K. M. Popov,et al.  Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites. , 2001, The Biochemical journal.

[74]  W. C. Hallows,et al.  Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases , 2006, Proceedings of the National Academy of Sciences.

[75]  Xiang Li,et al.  Examining post‐translational modification‐mediated protein–protein interactions using a chemical proteomics approach , 2013, Protein science : a publication of the Protein Society.

[76]  M. Mann,et al.  Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. , 2009, Molecular cell.

[77]  J. Hollander,et al.  Proteomic remodeling of mitochondria in heart failure. , 2011, Congestive heart failure.

[78]  Z. Papp,et al.  Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins. , 2003, Cardiovascular research.

[79]  J. Hoerter,et al.  Subcellular creatine kinase alterations. Implications in heart failure. , 1999, Circulation research.

[80]  Florian Gnad,et al.  Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif. , 2010, Molecular cell.

[81]  P. Rabinovitch,et al.  Mitochondria and cardiovascular aging. , 2012, Circulation research.

[82]  Adam R. Wende,et al.  Post‐translational modifications of the cardiac proteome in diabetes and heart failure , 2015, Proteomics. Clinical applications.

[83]  M. Gucek,et al.  What can we learn about cardioprotection from the cardiac mitochondrial proteome? , 2010, Cardiovascular research.

[84]  M. Cho,et al.  Protective Effects of Peroxiredoxin on Hydrogen Peroxide Induced Oxidative Stress and Apoptosis in Cardiomyocytes , 2012, Korean circulation journal.

[85]  K. Shimada,et al.  Early Statin Treatment in Patients With Acute Coronary Syndrome: Demonstration of the Beneficial Effect on Atherosclerotic Lesions by Serial Volumetric Intravascular Ultrasound Analysis During Half a Year After Coronary Event: The ESTABLISH Study , 2004, Circulation.

[86]  A. Levey,et al.  Proteomics of protein post-translational modifications implicated in neurodegeneration , 2014, Translational Neurodegeneration.

[87]  Albert J R Heck,et al.  Identification of enriched PTM crosstalk motifs from large-scale experimental data sets. , 2014, Journal of proteome research.

[88]  Harlan M Krumholz,et al.  National and regional trends in heart failure hospitalization and mortality rates for Medicare beneficiaries, 1998-2008. , 2011, JAMA.

[89]  M. Mann,et al.  Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. , 2014, Cell reports.

[90]  H. Zou,et al.  An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. , 2014, Journal of proteomics.

[91]  D. Galati,et al.  Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusion , 2007, FEBS letters.

[92]  Danica Chen,et al.  Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. , 2010, Cell metabolism.

[93]  J. Kemper Regulation of FXR transcriptional activity in health and disease: Emerging roles of FXR cofactors and post-translational modifications. , 2011, Biochimica et biophysica acta.

[94]  M. Patel,et al.  Regulation of the pyruvate dehydrogenase complex. , 2006, Biochemical Society transactions.

[95]  R. Hajjar,et al.  Differential Activation of Signal Transduction Pathways in Human Hearts With Hypertrophy Versus Advanced Heart Failure , 2001, Circulation.

[96]  F. Melchior,et al.  Concepts in sumoylation: a decade on , 2007, Nature Reviews Molecular Cell Biology.

[97]  Domenico de Rasmo,et al.  Mammalian complex I: a regulable and vulnerable pacemaker in mitochondrial respiratory function. , 2008, Biochimica et biophysica acta.

[98]  R. Korthuis,et al.  Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs preconditioning , 2014, Redox biology.

[99]  T. Ferro,et al.  Sp1: regulation of gene expression by phosphorylation. , 2005, Gene.

[100]  J. Balligand,et al.  Reversible S-nitrosation of creatine kinase by nitric oxide in adult rat ventricular myocytes. , 1998, Journal of molecular and cellular cardiology.

[101]  Melanie Y. White,et al.  Functional decorations: post-translational modifications and heart disease delineated by targeted proteomics , 2013, Genome Medicine.

[102]  T. Hunter,et al.  The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification 1 , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[103]  C. Brenner,et al.  Mitochondrial protein acetylation as a cell-intrinsic, evolutionary driver of fat storage: Chemical and metabolic logic of acetyl-lysine modifications , 2013, Critical reviews in biochemistry and molecular biology.

[104]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[105]  Predrag Radivojac,et al.  The structural and functional signatures of proteins that undergo multiple events of post‐translational modification , 2014, Protein science : a publication of the Protein Society.

[106]  Mulchand S Patel,et al.  Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases , 2001, Experimental & Molecular Medicine.

[107]  Y. Xiong,et al.  Glyceraldehyde-3-phosphate Dehydrogenase Is Activated by Lysine 254 Acetylation in Response to Glucose Signal* , 2013, The Journal of Biological Chemistry.

[108]  J. Stamler,et al.  Regulated Protein Denitrosylation by Cytosolic and Mitochondrial Thioredoxins , 2008, Science.

[109]  K. M. Popov,et al.  Diversity of the Pyruvate Dehydrogenase Kinase Gene Family in Humans * , 1995, The Journal of Biological Chemistry.

[110]  R. Scarpulla,et al.  cAMP-dependent Phosphorylation of the Nuclear Encoded 18-kDa (IP) Subunit of Respiratory Complex I and Activation of the Complex in Serum-starved Mouse Fibroblast Cultures* , 2000, The Journal of Biological Chemistry.

[111]  B. Song,et al.  Inhibition of mitochondrial aldehyde dehydrogenase by nitric oxide‐mediated S‐nitrosylation , 2005, FEBS letters.

[112]  U. Schmidt,et al.  Human heart failure: cAMP stimulation of SR Ca2+-ATPase activity and phosphorylation level of phospholamban. , 1999, American journal of physiology. Heart and circulatory physiology.

[113]  V. Figueredo,et al.  Direct evidence for inhibition of mitochondrial permeability transition pore opening by sevoflurane preconditioning in cardiomyocytes: comparison with cyclosporine A. , 2012, European journal of pharmacology.

[114]  A. Wiederkehr,et al.  Pyruvate dehydrogenase E1α phosphorylation is induced by glucose but does not control metabolism-secretion coupling in INS-1E clonal β-cells. , 2012, Biochimica et biophysica acta.

[115]  T. Hurd,et al.  Glutathionylation of mitochondrial proteins. , 2005, Antioxidants & redox signaling.

[116]  H. Lee,et al.  Trends in Ischemic Heart Disease Mortality in Korea, 1985-2009: An Age-period-cohort Analysis , 2012, Journal of preventive medicine and public health = Yebang Uihakhoe chi.

[117]  A. Halestrap,et al.  The regulation of branched-chain 2-oxo acid dehydrogenase of liver, kidney and heart by phosphorylation. , 1981, The Biochemical journal.

[118]  S. Snyder,et al.  Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[119]  M. Horikoshi,et al.  Simple histone acetylation plays a complex role in the regulation of gene expression. , 2006, Briefings in functional genomics & proteomics.

[120]  E. Iliodromitis,et al.  Ischemic preconditioning: Protection against myocardial necrosis and apoptosis , 2007, Vascular health and risk management.

[121]  Hanno Steen,et al.  Post‐translational modification: nature's escape from genetic imprisonment and the basis for dynamic information encoding , 2012, Wiley interdisciplinary reviews. Systems biology and medicine.

[122]  L. Johnson The regulation of protein phosphorylation. , 2009, Biochemical Society transactions.

[123]  M. Hirschey,et al.  Mitochondrial protein acetylation regulates metabolism. , 2012, Essays in biochemistry.

[124]  R. Balaban,et al.  Regulation of oxidative phosphorylation complex activity: effects of tissue-specific metabolic stress within an allometric series and acute changes in workload. , 2012, American journal of physiology. Regulatory, integrative and comparative physiology.

[125]  Matthew J. Rardin,et al.  SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. , 2013, Cell metabolism.

[126]  Xin-Yun Huang,et al.  SUMOylation-regulated Protein Phosphorylation, Evidence from Quantitative Phosphoproteomics Analyses* , 2011, The Journal of Biological Chemistry.

[127]  M. Mann,et al.  Brain phosphoproteome obtained by a FASP-based method reveals plasma membrane protein topology. , 2010, Journal of proteome research.

[128]  D. Barford Protein Phosphatases , 2004, Topics in Current Genetics.

[129]  R. Panizzutti,et al.  Inhibition of creatine kinase by S‐nitrosoglutathione , 1996, FEBS letters.

[130]  R. Jennings,et al.  Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. , 1986, Circulation.

[131]  T. Hurd,et al.  Disulphide formation on mitochondrial protein thiols. , 2005, Biochemical Society transactions.

[132]  G. Shore,et al.  Mitochondrial cytochrome c oxidase subunit IV is phosphorylated by an endogenous kinase , 1997, FEBS letters.

[133]  Yong Chen,et al.  SIRT3‐dependent deacetylation exacerbates acetaminophen hepatotoxicity , 2011, EMBO reports.

[134]  P. dos Santos,et al.  Alteration of mitochondrial function in a model of chronic ischemia in vivo in rat heart. , 2002, American journal of physiology. Heart and circulatory physiology.

[135]  C. Hoppel,et al.  Mitochondrial dysfunction in heart failure , 2013, Heart Failure Reviews.

[136]  Jianchun Dong,et al.  Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1. , 2003, European journal of biochemistry.

[137]  S. Ryter,et al.  Thioredoxin catalyzes the denitrosation of low-molecular mass and protein S-nitrosothiols. , 2007, Biochemistry.

[138]  P. J. Randle,et al.  Mechanism of activation of pyruvate dehydrogenase by dichloroacetate and other halogenated carboxylic acids. , 1974, The Biochemical journal.

[139]  C. Glass,et al.  Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. , 2006, Genes & development.

[140]  D. Choi,et al.  Treatment of Heart Failure with Reduced Ejection Fraction: Current Update , 2015 .

[141]  Shujian Wei,et al.  Acetylation‐dependent regulation of mitochondrial ALDH2 activation by SIRT3 mediates acute ethanol‐induced eNOS activation , 2012, FEBS letters.

[142]  E. R. Taylor,et al.  Glutaredoxin 2 Catalyzes the Reversible Oxidation and Glutathionylation of Mitochondrial Membrane Thiol Proteins , 2004, Journal of Biological Chemistry.

[143]  M. Mann,et al.  Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions , 2009, Science.

[144]  Yin-kun Liu,et al.  Identification of tyrosine-phosphorylated proteins associated with metastasis and functional analysis of FER in human hepatocellular carcinoma cells , 2009, BMC Cancer.

[145]  M. Laakso,et al.  Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis , 2011, Circulation research.

[146]  B. O’Malley,et al.  Multi-modulation of nuclear receptor coactivators through posttranslational modifications , 2009, Trends in Endocrinology & Metabolism.

[147]  B. O’Rourke,et al.  Mitochondrial protein phosphorylation as a regulatory modality: implications for mitochondrial dysfunction in heart failure. , 2011, Congestive heart failure.

[148]  Shiwei Song,et al.  A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis , 2008, Proceedings of the National Academy of Sciences.

[149]  Mark D Johnson,et al.  Proteomic Analysis in the Neurosciences* , 2002, Molecular & Cellular Proteomics.

[150]  N. Hogg,et al.  S-Nitrosothiols: cellular formation and transport. , 2005, Free radical biology & medicine.

[151]  Jeffrey Robbins,et al.  Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death , 2005, Nature.

[152]  Wang Wang,et al.  Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. , 2013, Cell metabolism.

[153]  D. Mochly‐Rosen,et al.  Reperfusion-Induced Translocation of &dgr;PKC to Cardiac Mitochondria Prevents Pyruvate Dehydrogenase Reactivation , 2005, Circulation research.

[154]  R. Cole,et al.  The Cardiac Acetyl-Lysine Proteome , 2013, PloS one.

[155]  S. Ficarro,et al.  cAMP-dependent Tyrosine Phosphorylation of Subunit I Inhibits Cytochrome c Oxidase Activity* , 2005, Journal of Biological Chemistry.

[156]  Robert A. Harris,et al.  Molecular defects in the E1α subunit of the branched-chain α-ketoacid dehydrogenase complex that cause maple syrup urine disease , 1991 .

[157]  Bramahn . Singh,et al.  Metabolic Modulators for Chronic Cardiac Ischemia , 2005, Journal of cardiovascular pharmacology and therapeutics.