Skip to main content
SpringerLink
Log in

Phosphorylation of Mammalian Cytochrome c and Cytochrome c Oxidase in the Regulation of Cell Destiny: Respiration, Apoptosis, and Human Disease

  • Chapter
  • First Online:
Mitochondrial Oxidative Phosphorylation

Part of the book series: Advances in Experimental Medicine and Biology ((volume 748))

Abstract

The mitochondrial oxidative phosphorylation (OxPhos) system not only generates the vast majority of cellular energy, but is also involved in the generation of reactive oxygen species (ROS), and apoptosis. Cytochrome c (Cytc) and cytochrome c oxidase (COX) represent the terminal step of the electron transport chain (ETC), the proposed rate-limiting reaction in mammals. Cytc and COX show unique regulatory features including allosteric regulation, isoform expression, and regulation through cell signaling pathways. This chapter focuses on the latter and discusses all mapped phosphorylation sites based on the crystal structures of COX and Cytc. Several signaling pathways have been identified that target COX including protein kinase A and C, receptor tyrosine kinase, and inflammatory signaling. In addition, four phosphorylation sites have been mapped on Cytc with potentially large implications due to its multiple functions including apoptosis, a pathway that is overactive in stressed cells but inactive in cancer. The role of COX and Cytc phosphorylation is reviewed in a human disease context, including cancer, inflammation, sepsis, asthma, and ischemia/reperfusion injury as seen in myocardial infarction and ischemic stroke.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acin-Perez R, Bayona-Bafaluy MP, Bueno M, Machicado C, Fernandez-Silva P, Perez-Martos A, Montoya J, Lopez-Perez MJ, Sancho J, Enriquez JA (2003) An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA. Hum Mol Genet 12:329–339

    PubMed  CAS  Google Scholar 

  • Acin-Perez R, Salazar E, Kamenetsky M, Buck J, Levin LR, Manfredi G (2009) Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation. Cell Metabolism 9:265–276

    PubMed  CAS  Google Scholar 

  • Arnold S, Goglia F, Kadenbach B (1998) 3,5-Diiodothyronine binds to subunit Va of cytochrome-c oxidase and abolishes the allosteric inhibition of respiration by ATP. Eur J Biochem 252:325–330

    PubMed  CAS  Google Scholar 

  • Aronowski J, Strong R, Grotta JC (1997) Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 17:1048–1056

    PubMed  CAS  Google Scholar 

  • Astiz M, Rackow EC, Weil MH, Schumer W (1988) Early impairment of oxidative metabolism and energy production in severe sepsis. Circ Shock 26:311–320

    PubMed  CAS  Google Scholar 

  • Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J 408:297–315

    PubMed  CAS  Google Scholar 

  • Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4:540–550

    PubMed  CAS  Google Scholar 

  • Baudouin SV, Saunders D, Tiangyou W, Elson JL, Poynter J, Pyle A, Keers S, Turnbull DM, Howell N, Chinnery PF (2005) Mitochondrial DNA and survival after sepsis: a prospective study. Lancet 366:2118–2121

    PubMed  Google Scholar 

  • Beauchemin AM, Gottlieb B, Beitel LK, Elhaji YA, Pinsky L, Trifiro MA (2001) Cytochrome c oxidase subunit Vb interacts with human androgen receptor: a potential mechanism for neurotoxicity in spinobulbar muscular atrophy. Brain Res Bull 56:285–297

    PubMed  CAS  Google Scholar 

  • Bender E, Kadenbach B (2000) The allosteric ATP-inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP-dependent phosphorylation. FEBS Lett 466:130–134

    PubMed  CAS  Google Scholar 

  • Boerner JL, Demory ML, Silva C, Parsons SJ (2004) Phosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II. Mol Cell Biol 24:7059–7071

    PubMed  CAS  Google Scholar 

  • Budas GR, Churchill EN, Disatnik MH, Sun L, Mochly-Rosen D (2010) Mitochondrial import of PKCepsilon is mediated by HSP90: a role in cardioprotection from ischaemia and reperfusion injury. Cardiovasc Res 88:83–92

    PubMed  CAS  Google Scholar 

  • Callahan LA, Supinski GS (2005) Downregulation of diaphragm electron transport chain and glycolytic enzyme gene expression in sepsis. J Appl Physiol 99:1120–1126

    PubMed  Google Scholar 

  • Campbell CA, Przyklenk K, Kloner RA (1986) Infarct size reduction: a review of the clinical trials. J Clin Pharmacol 26:317–329

    PubMed  CAS  Google Scholar 

  • Churchill EN, Szweda LI (2005) Translocation of deltaPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function. Arch Biochem Biophys 439:194–199

    PubMed  CAS  Google Scholar 

  • Dalmonte ME, Forte E, Genova ML, Giuffre A, Sarti P, Lenaz G (2009) Control of respiration by cytochrome c oxidase in intact cells: role of the membrane potential. J Biol Chem 284:32331–32335

    PubMed  CAS  Google Scholar 

  • Della-Morte D, Raval AP, Dave KR, Lin HW, Perez-Pinzon MA (2011) Post-ischemic activation of protein kinase C epsilon protects the hippocampus from cerebral ischemic injury via alterations in cerebral blood flow. Neurosci Lett 487:158–162

    PubMed  CAS  Google Scholar 

  • Demory ML, Boerner JL, Davidson R, Faust W, Miyake T, Lee I, Hüttemann M, Douglas R, Haddad G, Parsons SJ (2009) Epidermal growth factor receptor translocation to the mitochondria: regulation and effect. J Biol Chem 284:36592–36604

    PubMed  CAS  Google Scholar 

  • Dong S, Teng Z, Lu FH, Zhao YJ, Li H, Ren H, Chen H, Pan ZW, Lv YJ, Yang BF, Tian Y, Xu CQ, Zhang WH (2010) Post-conditioning protects cardiomyocytes from apoptosis via PKC(epsilon)-interacting with calcium-sensing receptors to inhibit endo(sarco)plasmic reticulum-mitochondria crosstalk. Mol Cell Biochem 341:195–206

    PubMed  CAS  Google Scholar 

  • Duvigneau JC, Piskernik C, Haindl S, Kloesch B, Hartl RT, Hüttemann M, Lee I, Ebel T, Moldzio R, Gemeiner M, Redl H, Kozlov AV (2008) A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction. Lab Invest 88:70–77

    PubMed  CAS  Google Scholar 

  • Ekholm A, Katsura K, Kristian T, Liu M, Folbergrova J, Siesjo BK (1993) Coupling of cellular energy state and ion homeostasis during recovery following brain ischemia. Brain Res 604:185–191

    PubMed  CAS  Google Scholar 

  • Fabian RH, DeWitt DS, Kent TA (1995) In vivo detection of superoxide anion production by the brain using a cytochrome c electrode. J Cereb Blood Flow Metab 15:242–247

    PubMed  CAS  Google Scholar 

  • Fang JK, Prabu SK, Sepuri NB, Raza H, Anandatheerthavarada HK, Galati D, Spear J, Avadhani NG (2007) Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusion. FEBS Lett 581:1302–1310

    PubMed  CAS  Google Scholar 

  • Fellman V, Raivio KO (1997) Reperfusion injury as the mechanism of brain damage after perinatal asphyxia. Pediatr Res 41:599–606

    PubMed  CAS  Google Scholar 

  • Ferguson-Miller S, Brautigan DL, Margoliash E (1976) Correlation of the kinetics of electron transfer activity of various eukaryotic cytochromes c with binding to mitochondrial cytochrome c oxidase. J Biol Chem 251:1104–1115

    PubMed  CAS  Google Scholar 

  • Fink MP (2002) Bench-to-bedside review: cytopathic hypoxia. Crit Care 6:491–499

    PubMed  Google Scholar 

  • Fiskum G, Rosenthal RE, Vereczki V, Martin E, Hoffman GE, Chinopoulos C, Kowaltowski A (2004) Protection against ischemic brain injury by inhibition of mitochondrial oxidative stress. J Bioenerg Biomembr 36:347–352

    PubMed  CAS  Google Scholar 

  • Giorgio M, Migliaccio E, Orsini F, Paolucci D, Moroni M, Contursi C, Pelliccia G, Luzi L, Minucci S, Marcaccio M, Pinton P, Rizzuto R, Bernardi P, Paolucci F, Pelicci PG (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122:221–233

    PubMed  CAS  Google Scholar 

  • Goldberg E, Sberna D, Wheat TE, Urbanski GJ, Margoliash E (1977) Cytochrome c: immunofluorescent localization of the testis-specific form. Science 196:1010–1012

    PubMed  CAS  Google Scholar 

  • Grivennikov SI, Karin M (2010) Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 21:11–19

    PubMed  CAS  Google Scholar 

  • Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899

    PubMed  CAS  Google Scholar 

  • Guo D, Nguyen T, Ogbi M, Tawfik H, Ma G, Yu Q, Caldwell RW, Johnson JA (2007) Protein kinase C-epsilon coimmunoprecipitates with cytochrome oxidase subunit IV and is associated with improved cytochrome-c oxidase activity and cardioprotection. Am J Physiol Heart Circ Physiol 293:H2219–H2230

    PubMed  CAS  Google Scholar 

  • Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35:505–513

    PubMed  CAS  Google Scholar 

  • Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D (1994) Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 330:1717–1722

    PubMed  CAS  Google Scholar 

  • Helling S, Vogt S, Rhiel A, Ramzan R, Wen L, Marcus K, Kadenbach B (2008) Phosphorylation and kinetics of mammalian cytochrome c oxidase. Mol Cell Proteomics 7:1714–1724

    PubMed  CAS  Google Scholar 

  • Hinkle PC, Kumar MA, Resetar A, Harris DL (1991) Mechanistic stoichiometry of mitochondrial oxidative phosphorylation. Biochemistry 30:3576–3582

    PubMed  CAS  Google Scholar 

  • Hopper RK, Carroll S, Aponte AM, Johnson DT, French S, Shen RF, Witzmann FA, Harris RA, Balaban RS (2006) Mitochondrial matrix phosphoproteome: effect of extra mitochondrial calcium. Biochemistry 45:2524–2536

    PubMed  CAS  Google Scholar 

  • Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348:138–150

    PubMed  CAS  Google Scholar 

  • Hüttemann M, Jaradat S, Grossman LI (2003) Cytochrome c oxidase of mammals contains a testes-specific isoform of subunit VIb – the counterpart to testes-specific cytochrome c? Mol Reprod Dev 66:8–16

    PubMed  Google Scholar 

  • Hüttemann M, Lee I, Samavati L, Yu H, Doan JW (2007) Regulation of mitochondrial oxidative phosphorylation through cell signaling. Biochim Biophys Acta 1773:1701–1720

    PubMed  Google Scholar 

  • Hüttemann M, Lee I, Pecinova A, Pecina P, Przyklenk K, Doan JW (2008) Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease. J Bioenerg Biomembr 40:445–456

    PubMed  Google Scholar 

  • Hüttemann M, Nantwi KD, Lee I, Liu J, Mohiuddin S, Petrov T (2010) Theophylline treatment improves mitochondrial function after upper cervical spinal cord hemisection. Exp Neurol 223:523–528

    PubMed  Google Scholar 

  • Hüttemann M, Helling S, Sanderson TH, Sinkler C, Samavati L, Mahapatra G, Varughese A, Lu G, Liu J, Ramzan R, Vogt S, Grossman LI, Doan JW, Marcus K, Lee I (2012) Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. Biochim Biophys Acta 1817:598–609

    Google Scholar 

  • Hüttemann M, Pecina P, Rainbolt M, Sanderson TH, Kagan VE, Samavati L, Doan JW, Lee I (2011) The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from respiration to apoptosis. Mitochondrion 11:369–381

    PubMed  Google Scholar 

  • Kagan VE, Bayir HA, Belikova NA, Kapralov O, Tyurina YY, Tyurin VA, Jiang J, Stoyanovsky DA, Wipf P, Kochanek PM, Greenberger JS, Pitt B, Shvedova AA, Borisenko G (2009) Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radic Biol Med 46:1439–1453

    PubMed  CAS  Google Scholar 

  • Kamp DW, Shacter E, Weitzman SA (2011) Chronic inflammation and cancer: the role of the mitochondria. Oncology 25:400–410, 413

    Google Scholar 

  • Kim J, Takeuchi H, Lam ST, Turner RR, Wang HJ, Kuo C, Foshag L, Bilchik AJ, Hoon DS (2005) Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol 23:2744–2753

    PubMed  CAS  Google Scholar 

  • Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457:102–106

    PubMed  CAS  Google Scholar 

  • Kirichenko A, Vygodina T, Mkrtchyan HM, Konstantinov A (1998) Specific cation binding site in mammalian cytochrome oxidase. FEBS Lett 423:329–333

    PubMed  CAS  Google Scholar 

  • Kirichenko AV, Pfitzner U, Ludwig B, Soares CM, Vygodina TV, Konstantinov AA (2005) Cytochrome c oxidase as a calcium binding protein. Studies on the role of a conserved aspartate in helices XI-XII cytoplasmic loop in cation binding. Biochemistry 44:12391–12401

    PubMed  CAS  Google Scholar 

  • Knab S, Mushak TM, Schmitz-Esser S, Horn M, Haferkamp I (2011) Nucleotide parasitism by Simkania negevensis (Chlamydiae). J Bacteriol 193:225–235

    PubMed  CAS  Google Scholar 

  • Ko YH, Pan W, Inoue C, Pedersen PL (2002) Signal transduction to mitochondrial ATP synthase: evidence that PDGF-dependent phosphorylation of the delta-subunit occurs in several cell lines, involves tyrosine, and is modulated by lysophosphatidic acid. Mitochondrion 1:339–348

    PubMed  CAS  Google Scholar 

  • Korshunov SS, Krasnikov BF, Pereverzev MO, Skulachev VP (1999) The antioxidant functions of cytochrome c. FEBS Lett 462:192–198

    PubMed  CAS  Google Scholar 

  • Kowalczyk JE, Kawalec M, Beresewicz M, Debski J, Dadlez M, Zablocka B (2012) Protein kinase C beta in postischemic brain mitochondria. Mitochondrion 12(1):138–143

    PubMed  CAS  Google Scholar 

  • Kulbe H, Hagemann T, Szlosarek PW, Balkwill FR, Wilson JL (2005) The inflammatory cytokine tumor necrosis factor-alpha regulates chemokine receptor expression on ovarian cancer cells. Cancer Res 65:10355–10362

    PubMed  CAS  Google Scholar 

  • Lee I, Kadenbach B (2001) Palmitate decreases proton pumping of liver-type cytochrome c oxidase. Eur J Biochem 268:6329–6334

    PubMed  CAS  Google Scholar 

  • Lee MD, Zentella A, Vine W, Pekala PH, Cerami A (1987) Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6. Proc Natl Acad Sci USA 84:2590–2594

    PubMed  CAS  Google Scholar 

  • Lee I, Bender E, Kadenbach B (2002) Control of mitochondrial membrane potential and ROS formation by reversible phosphorylation of cytochrome c oxidase. Mol Cell Biochem 234–235:63–70

    PubMed  Google Scholar 

  • Lee I, Salomon AR, Ficarro S, Mathes I, Lottspeich F, Grossman LI, Hüttemann M (2005) cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity. J Biol Chem 280:6094–6100

    PubMed  CAS  Google Scholar 

  • Lee I, Salomon AR, Yu K, Doan JW, Grossman LI, Hüttemann M (2006) New prospects for an old enzyme: mammalian cytochrome c is tyrosine-phosphorylated in vivo. Biochemistry 45:9121–9128

    PubMed  CAS  Google Scholar 

  • Lee I, Pecinova A, Pecina P, Neel BG, Araki T, Kucherlapati R, Roberts AE, Hüttemann M (2010) A suggested role for mitochondria in Noonan syndrome. Biochim Biophys Acta 1802:275–283

    PubMed  CAS  Google Scholar 

  • Levy RJ, Vijayasarathy C, Raj NR, Avadhani NG, Deutschman CS (2004) Competitive and noncompetitive inhibition of myocardial cytochrome c oxidase in sepsis. Shock 21:110–114

    PubMed  CAS  Google Scholar 

  • Liu SS (1999) Cooperation of a “reactive oxygen cycle” with the Q cycle and the proton cycle in the respiratory chain–superoxide generating and cycling mechanisms in mitochondria. J Bioenerg Biomembr 31:367–376

    PubMed  CAS  Google Scholar 

  • Liu RR, Murphy TH (2009) Reversible cyclosporin A-sensitive mitochondrial depolarization occurs within minutes of stroke onset in mouse somatosensory cortex in vivo: a two-photon imaging study. J Biol Chem 284:36109–36117

    PubMed  CAS  Google Scholar 

  • Liu Z, Lin H, Ye S, Liu QY, Meng Z, Zhang CM, Xia Y, Margoliash E, Rao Z, Liu XJ (2006) Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis. Proc Natl Acad Sci USA 103:8965–8970

    PubMed  CAS  Google Scholar 

  • Lorente L, Martin MM, Lopez-Gallardo E, Iceta R, Sole-Violan J, Blanquer J, Labarta L, Diaz C, Jimenez A, Lafuente N, Hernandez M, Mendez F, Medina N, Ferrer-Aguero JM, Ferreres J, Llimiñana MC, Mora ML, Lubillo S, Sanchez-Palacios M, Montoya J, Ruiz-Pesini E (2011) Platelet cytochrome c oxidase activity and quantity in septic patients. Crit Care Med 39:1289–1294

    PubMed  CAS  Google Scholar 

  • Lu N, Wang W, Liu J, Wong CW (2011) Protein kinase C epsilon affects mitochondrial function through estrogen-related receptor alpha. Cell Signal 23(9):1473–1478

    PubMed  CAS  Google Scholar 

  • Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    PubMed  CAS  Google Scholar 

  • Martinez-Ruiz A, Cadenas S, Lamas S (2011) Nitric oxide signaling: classical, less classical, and nonclassical mechanisms. Free Radic Biol Med 51:17–29

    PubMed  CAS  Google Scholar 

  • Miyazaki T, Neff L, Tanaka S, Horne WC, Baron R (2003) Regulation of cytochrome c oxidase activity by c-Src in osteoclasts. J Cell Biol 160:709–718

    PubMed  CAS  Google Scholar 

  • Neel BG, Gu H, Pao L (2003) The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 28:284–293

    PubMed  CAS  Google Scholar 

  • Ogbi M, Johnson JA (2006) Protein kinase Cε interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning. Biochem J 393:191–199

    PubMed  CAS  Google Scholar 

  • Ogbi M, Chew CS, Pohl J, Stuchlik O, Ogbi S, Johnson JA (2004) Cytochrome c oxidase subunit IV as a marker of protein kinase Cε function in neonatal cardiac myocytes: implications for cytochrome c oxidase activity. Biochem J 382:923–932

    PubMed  CAS  Google Scholar 

  • Oliver CN, Starke-Reed PE, Stadtman ER, Liu GJ, Carney JM, Floyd RA (1990) Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc Natl Acad Sci USA 87:5144–5147

    PubMed  CAS  Google Scholar 

  • Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3:ra3

    PubMed  Google Scholar 

  • Pacelli C, Latorre D, Cocco T, Capuano F, Kukat C, Seibel P, Villani G (2011) Tight control of mitochondrial membrane potential by cytochrome c oxidase. Mitochondrion 11:334–341

    PubMed  CAS  Google Scholar 

  • Pang L, Qiu T, Cao X, Wan M (2011) Apoptotic role of TGF-beta mediated by Smad4 mitochondria translocation and cytochrome c oxidase subunit II interaction. Exp Cell Res 317:1608–1620

    PubMed  CAS  Google Scholar 

  • Pecina P, Borisenko GG, Belikova NA, Tyurina YY, Pecinova A, Lee I, Samhan-Arias AK, Przyklenk K, Kagan VE, Hüttemann M (2010) Phosphomimetic substitution of cytochrome c tyrosine 48 decreases respiration and binding to cardiolipin and abolishes ability to trigger downstream caspase activation. Biochemistry 49:6705–6714

    PubMed  CAS  Google Scholar 

  • Pedersen PL (1978) Tumor mitochondria and the bioenergetics of cancer cells. Prog Exp Tumor Res 22:190–274

    PubMed  CAS  Google Scholar 

  • Persichini T, Mazzone V, Polticelli F, Moreno S, Venturini G, Clementi E, Colasanti M (2005) Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neurosci Lett 384:254–259

    PubMed  CAS  Google Scholar 

  • Piantadosi CA, Zhang J (1996) Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. Stroke 27:327–332

    PubMed  CAS  Google Scholar 

  • Picard M, Taivassalo T, Ritchie D, Wright KJ, Thomas MM, Romestaing C, Hepple RT (2011) Mitochondrial structure and function are disrupted by standard isolation methods. PLoS One 6:e18317

    PubMed  CAS  Google Scholar 

  • Piccoli C, Scrima R, Boffoli D, Capitanio N (2006) Control by cytochrome c oxidase of the cellular oxidative phosphorylation system depends on the mitochondrial energy state. Biochem J 396:573–583

    PubMed  CAS  Google Scholar 

  • Prabu SK, Anandatheerthavarada HK, Raza H, Srinivasan S, Spear JF, Avadhani NG (2006) Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury. J Biol Chem 281:2061–2070

    PubMed  CAS  Google Scholar 

  • Rakoff-Nahoum S (2006) Why cancer and inflammation? Yale J Biol Med 79:123–130

    PubMed  CAS  Google Scholar 

  • Ralph SJ, Rodriguez-Enriquez S, Neuzil J, Saavedra E, Moreno-Sanchez R (2010) The causes of cancer revisited: “mitochondrial malignancy” and ROS-induced oncogenic transformation – why mitochondria are targets for cancer therapy. Mol Aspects Med 31:145–170

    PubMed  CAS  Google Scholar 

  • Revelly JP, Tappy L, Martinez A, Bollmann M, Cayeux MC, Berger MM, Chiolero RL (2005) Lactate and glucose metabolism in severe sepsis and cardiogenic shock. Crit Care Med 33:2235–2240

    PubMed  CAS  Google Scholar 

  • Robb-Gaspers LD, Burnett P, Rutter GA, Denton RM, Rizzuto R, Thomas AP (1998) Integrating cytosolic calcium signals into mitochondrial metabolic responses. EMBO J 17:4987–5000

    PubMed  CAS  Google Scholar 

  • Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J (2011) Heart disease and stroke statistics – 2011 update: a report from the American Heart Association. Circulation 123:e18–e209

    PubMed  Google Scholar 

  • Rosenthal RE, Hamud F, Fiskum G, Varghese PJ, Sharpe S (1987) Cerebral ischemia and reperfusion: prevention of brain mitochondrial injury by lidoflazine. J Cereb Blood Flow Metab 7:752–758

    PubMed  CAS  Google Scholar 

  • Ruggieri AJ, Levy RJ, Deutschman CS (2010) Mitochondrial dysfunction and resuscitation in sepsis. Crit Care Clin 26:567–575, x–xi

    Google Scholar 

  • Salvi M, Brunati AM, Bordin L, La Rocca N, Clari G, Toninello A (2002) Characterization and location of Src-dependent tyrosine phosphorylation in rat brain mitochondria. Biochim Biophys Acta 1589:181–195

    PubMed  CAS  Google Scholar 

  • Salvi M, Stringaro A, Brunati AM, Agostinelli E, Arancia G, Clari G, Toninello A (2004) Tyrosine phosphatase activity in mitochondria: presence of Shp-2 phosphatase in mitochondria. Cell Mol Life Sci 61:2393–2404

    PubMed  CAS  Google Scholar 

  • Samavati L, Lee I, Mathes I, Lottspeich F, Hüttemann M (2008) Tumor necrosis factor α inhibits oxidative phosphorylation through tyrosine phosphorylation at subunit I of cytochrome c oxidase. J Biol Chem 283:21134–21144

    PubMed  CAS  Google Scholar 

  • Sanishvili R, Volz KW, Westbrook EM, Margoliash E (1995) The low ionic strength crystal structure of horse cytochrome c at 2.1 Å resolution and comparison with its high ionic strength counterpart. Structure 3:707–716

    PubMed  CAS  Google Scholar 

  • Sivaraman V, Hausenloy DJ, Kolvekar S, Hayward M, Yap J, Lawrence D, Di Salvo C, Yellon DM (2009) The divergent roles of protein kinase C epsilon and delta in simulated ischaemia-reperfusion injury in human myocardium. J Mol Cell Cardiol 46:758–764

    PubMed  CAS  Google Scholar 

  • Steenaart NA, Shore GC (1997) Mitochondrial cytochrome c oxidase subunit IV is phosphorylated by an endogenous kinase. FEBS Lett 415:294–298

    PubMed  CAS  Google Scholar 

  • Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD (2001) Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29:465–468

    PubMed  CAS  Google Scholar 

  • Tartaglia M, Gelb BD, Zenker M (2011) Noonan syndrome and clinically related disorders. Best practice & research. J Clin Endocrinol Metab 25:161–179

    CAS  Google Scholar 

  • Thingholm TE, Jorgensen TJ, Jensen ON, Larsen MR (2006) Highly selective enrichment of phosphorylated peptides using titanium dioxide. Nat Protoc 1:1929–1935

    PubMed  CAS  Google Scholar 

  • Tilney NL, Guttmann RD (1997) Effects of initial ischemia/reperfusion injury on the transplanted kidney. Transplantation 64:945–947

    PubMed  CAS  Google Scholar 

  • Tracey KJ, Lowry SF, Fahey TJ, Albert JD, Fong Y, Hesse D, Beutler B, Manogue KR, Calvano S, Wei H, Cerami A, Shires GT (1987) Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet 164:415–422

    PubMed  CAS  Google Scholar 

  • Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S (1996) The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 Å. Science 272:1136–1144

    PubMed  CAS  Google Scholar 

  • Tsukihara T, Shimokata K, Katayama Y, Shimada H, Muramoto K, Aoyama H, Mochizuki M, Shinzawa-Itoh K, Yamashita E, Yao M, Ishimura Y, Yoshikawa S (2003) The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process. Proc Natl Acad Sci USA 100:15304–15309

    PubMed  CAS  Google Scholar 

  • Villani G, Attardi G (1997) In vivo control of respiration by cytochrome c oxidase in wild-type and mitochondrial DNA mutation-carrying human cells. Proc Natl Acad Sci USA 94:1166–1171

    PubMed  CAS  Google Scholar 

  • Villani G, Greco M, Papa S, Attardi G (1998) Low reserve of cytochrome c oxidase capacity in vivo in the respiratory chain of a variety of human cell types. J Biol Chem 273:31829–31836

    PubMed  CAS  Google Scholar 

  • Vlessis AA, Widener LL, Bartos D (1990) Effect of peroxide, sodium, and calcium on brain mitochondrial respiration in vitro: potential role in cerebral ischemia and reperfusion. J Neurochem 54:1412–1418

    PubMed  CAS  Google Scholar 

  • von Ballmoos C, Gennis RB, Adelroth P, Brzezinski P (2011) Kinetic design of the respiratory oxidases. Proc Natl Acad Sci USA 108:11057–11062

    Google Scholar 

  • von der Hocht I, van Wonderen JH, Hilbers F, Angerer H, MacMillan F, Michel H (2011) Interconversions of P and F intermediates of cytochrome c oxidase from Paracoccus denitrificans. Proc Natl Acad Sci USA 108:3964–3969

    PubMed  Google Scholar 

  • Walther TC, Mann M (2010) Mass spectrometry-based proteomics in cell biology. J Cell Biol 190:491–500

    PubMed  CAS  Google Scholar 

  • Wang ZB, Li M, Zhao Y, Xu JX (2003) Cytochrome c is a hydrogen peroxide scavenger in mitochondria. Protein Pept Lett 10:247–253

    PubMed  CAS  Google Scholar 

  • Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    PubMed  CAS  Google Scholar 

  • Warburg O, Posener K, Negelein E (1924) Über den Stoffwechsel der Carcinomzelle. Biochem Z 152:309–344

    CAS  Google Scholar 

  • Weinberg F, Chandel NS (2009) Mitochondrial metabolism and cancer. Ann N Y Acad Sci 1177:66–73

    PubMed  CAS  Google Scholar 

  • Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GR, Chandel NS (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 107:8788–8793

    PubMed  CAS  Google Scholar 

  • Welch EJ, Jones BW, Scott JD (2010) Networking with AKAPs: context-dependent regulation of anchored enzymes. Mol Interv 10:86–97

    PubMed  CAS  Google Scholar 

  • Yang WL, Iacono L, Tang WM, Chin KV (1998) Novel function of the regulatory subunit of protein kinase A: regulation of cytochrome c oxidase activity and cytochrome c release. Biochemistry 37:14175–14180

    PubMed  CAS  Google Scholar 

  • Yoshikawa S, Muramoto K, Shinzawa-Itoh K (2011) The O2 reduction and proton pumping gate mechanism of bovine heart cytochrome c oxidase. Biochim Biophys Acta 1807:1279–1286

    PubMed  CAS  Google Scholar 

  • Yu H, Lee I, Salomon AR, Yu K, Hüttemann M (2008a) Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting mitochondrial respiration. Biochim Biophys Acta 1777:1066–1071

    PubMed  CAS  Google Scholar 

  • Yu Q, Nguyen T, Ogbi M, Caldwell RW, Johnson JA (2008b) Differential loss of cytochrome-c oxidase subunits in ischemia-reperfusion injury: exacerbation of COI subunit loss by PKC-epsilon inhibition. Am J Physiol 294:H2637–H2645

    CAS  Google Scholar 

  • Zaidan E, Sims NR (1994) The calcium content of mitochondria from brain subregions following short-term forebrain ischemia and recirculation in the rat. J Neurochem 63:1812–1819

    PubMed  CAS  Google Scholar 

  • Zhang Z, Gerstein M (2003) The human genome has 49 cytochrome c pseudogenes, including a relic of a primordial gene that still functions in mouse. Gene 312:61–72

    PubMed  CAS  Google Scholar 

  • Zhang S, Li H, Yang SJ (2010) Tribulosin protects rat hearts from ischemia/reperfusion injury. Acta Pharmacol Sin 31:671–678

    PubMed  Google Scholar 

  • Zhao X, Leon IR, Bak S, Mogensen M, Wrzesinski K, Hojlund K, Jensen ON (2010) Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes. Mol Cell Proteomics 10(1):M110.000299

    PubMed  Google Scholar 

  • Zweier JL (1988) Measurement of superoxide-derived free radicals in the reperfused heart. Evidence for a free radical mechanism of reperfusion injury. J Biol Chem 263:1353–1357

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grant GM089900 from the National Institutes of Health, a Department of Defence USAMRAA National Oncogenomic and Molecular Imaging Center contract through the Karmanos Cancer Institute, Detroit, the Center for Molecular Medicine and Genetics, and the Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit.

Author information

Authors and Affiliations

  1. Center for Molecular Medicine and Genetics, and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, USA

    Maik Hüttemann & Lawrence I. Grossman

  2. Karmanos Cancer Institute, Detroit, MI, USA

    Maik Hüttemann & Lawrence I. Grossman

  3. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Icksoo Lee & Jeffrey W. Doan

  4. Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Thomas H. Sanderson

  5. Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Thomas H. Sanderson

Authors
  1. Maik Hüttemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Icksoo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence I. Grossman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey W. Doan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas H. Sanderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maik Hüttemann .

Editor information

Editors and Affiliations

  1. Philipps-Universitaet Marburg, Marburg, 35032, Germany

    Bernhard Kadenbach

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hüttemann, M., Lee, I., Grossman, L.I., Doan, J.W., Sanderson, T.H. (2012). Phosphorylation of Mammalian Cytochrome c and Cytochrome c Oxidase in the Regulation of Cell Destiny: Respiration, Apoptosis, and Human Disease. In: Kadenbach, B. (eds) Mitochondrial Oxidative Phosphorylation. Advances in Experimental Medicine and Biology, vol 748. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3573-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation