Skip to main content

Advertisement

SpringerLink
Log in

SIRT3 deficiency impairs mitochondrial and contractile function in the heart

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Sirtuin 3 (SIRT3) is a mitochondrial NAD+-dependent deacetylase that regulates energy metabolic enzymes by reversible protein lysine acetylation in various extracardiac tissues. The role of SIRT3 in myocardial energetics and in the development of mitochondrial dysfunction in cardiac pathologies, such as the failing heart, remains to be elucidated. To investigate the role of SIRT3 in the regulation of myocardial energetics and function SIRT3−/− mice developed progressive age-related deterioration of cardiac function, as evidenced by a decrease in ejection fraction and an increase in enddiastolic volume at 24 but not 8 weeks of age using echocardiography. Four weeks following transverse aortic constriction, ejection fraction was further decreased in SIRT3−/− mice compared to WT mice, accompanied by a greater degree of cardiac hypertrophy and fibrosis. In isolated working hearts, a decrease in cardiac function in SIRT3−/− mice was accompanied by a decrease in palmitate oxidation, glucose oxidation, and oxygen consumption, whereas rates of glycolysis were increased. Respiratory capacity and ATP synthesis were decreased in cardiac mitochondria of SIRT3−/− mice. HPLC measurements revealed a decrease of the myocardial ATP/AMP ratio and of myocardial energy charge. Using LC–MS/MS, we identified increased acetylation of 84 mitochondrial proteins, including 6 enzymes of fatty acid import and oxidation, 50 subunits of the electron transport chain, and 3 enzymes of the tricarboxylic acid cycle. Lack of SIRT3 impairs mitochondrial and contractile function in the heart, likely due to increased acetylation of various energy metabolic proteins and subsequent myocardial energy depletion.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

4-HNE:

4-hydroxynonenal

ACN:

Acetonitrile

ANT1:

Adenine nucleotide translocator 1

ATPase6:

ATP synthase F0 subunit 6

Cox II:

Cytochrome c oxidase subunit 2

Cox IV:

Cytochrome c oxidase subunit 4

Cpt:

Carnitine palmitoyltransferase

Errα:

Estrogen-related receptor alpha

FOXO3a:

Forkhead box O3a

GDH:

Glutamate dehydrogenase

Hadhβ:

Hydroxyacyl CoA dehydrogenase beta

KHB:

Krebs Henseleit buffer

Lcad:

Long-chain acyl-CoA dehydrogenase

Mcad:

Medium-chain acyl-CoA dehydrogenase

mt-Nd2:

NADH dehydrogenase 2, mitochondrial

MVO2 :

Myocardial oxygen consumption

Ndufv1:

NADH dehydrogenase [ubiquinone] flavoprotein 1

Ndufa9:

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9

Pparα:

Peroxisome proliferator-activated receptor alpha

Uqcrc1:

Ubiquinol cytochrome c reductase core protein 1

Nrf1:

Nuclear respiratory factor 1

Pgc-1α:

Peroxisome proliferator-activated receptor gamma coactivator 1 alpha

Pgc-1β:

Peroxisome proliferator-activated receptor gamma coactivator 1 beta

Sod2:

Manganese superoxide dismutase

Sdh1:

Succinate dehydrogenase flavoprotein subunit 1

TAC:

Transverse aortic constriction

Tfam:

Mitochondrial transcription factor A

References

  1. Aasum E, Hafstad AD, Severson DL, Larsen TS (2003) Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. Diabetes 52:434–441. doi:10.2337/diabetes.52.2.434

    Article  CAS  PubMed  Google Scholar 

  2. Acin A, Rodriguez M, Rique H, Canet E, Boutin JA, Galizzi JP (1999) Cloning and characterization of the 5′ flanking region of the human uncoupling protein 3 (UCP3) gene. Biochem Biophys Res Commun 258:278–283. doi:10.1006/bbrc.1999.0530

    Article  CAS  PubMed  Google Scholar 

  3. Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci USA 105:14447–14452. doi:10.1073/pnas.0803790105

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Alrob OA, Sankaralingam S, Ma C, Wagg CS, Fillmore N, Jaswal JS, Sack MN, Lehner R, Gupta MP, Michelakis ED, Padwal RS, Johnstone DE, Sharma AM, Lopaschuk GD (2014) Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling. Cardiovasc Res 103:485–497. doi:10.1093/cvr/cvu156

    Article  CAS  PubMed  Google Scholar 

  5. Aoyama T, Peters JM, Iritani N, Nakajima T, Furihata K, Hashimoto T, Gonzalez FJ (1998) Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha). J Biol Chem 273:5678–5684. doi:10.1074/jbc.273.10.5678

    Article  CAS  PubMed  Google Scholar 

  6. Boengler K, Schulz R, Heusch G (2009) Loss of cardioprotection with ageing. Cardiovasc Res 83:247–261. doi:10.1093/cvr/cvp033

    Article  CAS  PubMed  Google Scholar 

  7. Boudina S, Sena S, Theobald H, Sheng X, Wright JJ, Hu XX, Aziz S, Johnson JI, Bugger H, Zaha VG, Abel ED (2007) Mitochondrial energetics in the heart in obesity related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 56:2457–2466. doi:10.2337/db07-0481

    Article  CAS  PubMed  Google Scholar 

  8. Bugger H, Abel ED (2010) Mitochondria in the diabetic heart. Cardiovasc Res 88:229–240. doi:10.1093/cvr/cvq239

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Bugger H, Abel ED (2008) Molecular mechanisms for myocardial mitochondrial dysfunction in the metabolic syndrome. Clin Sci (Lond) 114:195–210. doi:10.1042/CS20070166

    Article  CAS  Google Scholar 

  10. Bugger H, Boudina S, Hu XX, Tuinei J, Zaha VG, Theobald HA, Yun UJ, McQueen AP, Wayment B, Litwin SE, Abel ED (2008) Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3. Diabetes 57:2924–2932. doi:10.2337/db08-0079

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Bugger H, Chen D, Riehle C, Soto J, Theobald HA, Hu XX, Ganesan B, Weimer BC, Abel ED (2009) Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice. Diabetes 58:1986–1997. doi:10.2337/db09-0259

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Bugger H, Schwarzer M, Chen D, Schrepper A, Amorim PA, Schoepe M, Nguyen TD, Mohr FW, Khalimonchuk O, Weimer BC, Doenst T (2010) Proteomic remodelling of mitochondrial oxidative pathways in pressure overload-induced heart failure. Cardiovasc Res 85:376–384. doi:10.1093/cvr/cvp344

    Article  CAS  PubMed  Google Scholar 

  13. Cimen H, Han MJ, Yang Y, Tong Q, Koc H, Koc EC (2010) Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 49:304–311. doi:10.1021/bi901627u

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415:96–99. doi:10.1038/415096a

    Article  CAS  PubMed  Google Scholar 

  15. Fiehn O (2006) Metabolite profiling in Arabidopsis. Methods Mol Biol 323:439–447. doi:10.1385/1-59745-003-0:439

    CAS  PubMed  Google Scholar 

  16. Graham BH, Waymire KG, Cottrell B, Trounce IA, MacGregor GR, Wallace DC (1997) A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator. Nat Genet 16:226–234. doi:10.1038/ng0797-226

    Article  CAS  PubMed  Google Scholar 

  17. Grillon JM, Johnson KR, Kotlo K, Danziger RS (2012) Non-histone lysine acetylated proteins in heart failure. Biochim Biophys Acta 1822:607–614. doi:10.1016/j.bbadis.2011.11.016

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, Sinclair DA (2010) Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY) 2:914–923 (100252 [pii])

    CAS  Google Scholar 

  19. Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ (2013) Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol Cell 49:186–199. doi:10.1016/j.molcel.2012.10.024

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB, Bain JR, Newgard CB, Farese RV Jr, Alt FW, Kahn CR, Verdin E (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121–125. doi:10.1038/nature08778

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Hsu CP, Oka S, Shao D, Hariharan N, Sadoshima J (2009) Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circ Res 105:481–491. doi:10.1161/CIRCRESAHA.109.203703

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Jaeger C, Tellström V, Zurek G, König S, Eimer S, Kammerer B (2014) Metabolomic changes in Caenorhabditis elegans lifespan mutants as evident from GC-EI-MS and GC-APCI-TOF-MS profiling. Metabolomics 10:859–876. doi:10.1007/s11306-014-0637-y

    Article  CAS  Google Scholar 

  23. Jeong SM, Xiao C, Finley LW, Lahusen T, Souza AL, Pierce K, Li YH, Wang X, Laurent G, German NJ, Xu X, Li C, Wang RH, Lee J, Csibi A, Cerione R, Blenis J, Clish CB, Kimmelman A, Deng CX, Haigis MC (2013) SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 23:450–463. doi:10.1016/j.ccr.2013.02.024

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Karamanlidis G, Lee CF, Garcia-Menendez L, Kolwicz SC Jr, Suthammarak W, Gong G, Sedensky MM, Morgan PG, Wang W, Tian R (2013) Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metab 18:239–250. doi:10.1016/j.cmet.2013.07.002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Kawahara Y, Tanonaka K, Daicho T, Nawa M, Oikawa R, Nasa Y, Takeo S (2005) Preferable anesthetic conditions for echocardiographic determination of murine cardiac function. J Pharmacol Sci 99:95–104. doi:10.1254/jphs.FP0050343

    Article  CAS  PubMed  Google Scholar 

  26. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, Wallace DC (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427:461–465. doi:10.1038/nature02229

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Lehman TC, Hale DE, Bhala A, Thorpe C (1990) An acyl-coenzyme A dehydrogenase assay utilizing the ferricenium ion. Anal Biochem 186:280–284

    Article  CAS  PubMed  Google Scholar 

  28. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27:8807–8814. doi:10.1128/MCB.01636-07

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Lu Z, Chen Y, Aponte AM, Battaglia V, Gucek M, Sack MN (2015) Prolonged fasting identifies heat shock protein 10 as a Sirtuin 3 substrate: elucidating a new mechanism linking mitochondrial protein acetylation to fatty acid oxidation enzyme folding and function. J Biol Chem 290:2466–2476. doi:10.1074/jbc.M114.606228

    Article  CAS  PubMed  Google Scholar 

  30. Marin-Garcia J (2003) Mitochondrial dysfunction in heart failure. J Am Coll Cardiol 41:229. doi:10.1016/S0735-1097(03)00494-7 (author reply 2299)

    Article  Google Scholar 

  31. Michan S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1–13. doi:10.1042/BJ20070140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Murray AJ, Cole MA, Lygate CA, Carr CA, Stuckey DJ, Little SE, Neubauer S, Clarke K (2008) Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart. J Mol Cell Cardiol 44:694–700. doi:10.1016/j.yjmcc.2008.01.008

    Article  CAS  PubMed  Google Scholar 

  33. Nakagawa T, Lomb DJ, Haigis MC, Guarente L (2009) SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137:560–570. doi:10.1016/j.cell.2009.02.026

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Narula N, Zaragoza MV, Sengupta PP, Li P, Haider N, Verjans J, Waymire K, Vannan M, Wallace DC (2011) Adenine nucleotide translocase 1 deficiency results in dilated cardiomyopathy with defects in myocardial mechanics, histopathological alterations, and activation of apoptosis. JACC Cardiovasc Imaging 4:1–10. doi:10.1016/j.jcmg.2010.06.018

    Article  PubMed Central  PubMed  Google Scholar 

  35. Nickel A, Loffler J, Maack C (2013) Myocardial energetics in heart failure. Basic Res Cardiol 108:358. doi:10.1007/s00395-013-0358-9

    Article  PubMed  Google Scholar 

  36. North BJ, Verdin E (2004) Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol 5:224. doi:10.1186/gb-2004-5-5-224

    Article  PubMed Central  PubMed  Google Scholar 

  37. Pacher P, Liaudet L, Mabley J, Komjati K, Szabo C (2002) Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure. J Am Coll Cardiol 40:1006–1016. doi:10.1016/S0735-1097(02)02062-4

    Article  CAS  PubMed  Google Scholar 

  38. Parodi-Rullan R, Barreto-Torres G, Ruiz L, Casasnovas J, Javadov S (2012) Direct renin inhibition exerts an anti-hypertrophic effect associated with improved mitochondrial function in post-infarction heart failure in diabetic rats. Cell Physiol Biochem 29:841–850. doi:10.1159/000178526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA, Ilkayeva O, Marcheva B, Kobayashi Y, Omura C, Levine DC, Bacsik DJ, Gius D, Newgard CB, Goetzman E, Chandel NS, Denu JM, Mrksich M, Bass J (2013) Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342:1243417. doi:10.1126/science.1243417

    Article  PubMed Central  PubMed  Google Scholar 

  40. Pillai JB, Isbatan A, Imai S, Gupta MP (2005) Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem 280:43121–43130. doi:10.1074/jbc.M506162200

    Article  CAS  PubMed  Google Scholar 

  41. Pillai VB, Sundaresan NR, Kim G, Gupta M, Rajamohan SB, Pillai JB, Samant S, Ravindra PV, Isbatan A, Gupta MP (2010) Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem 285:3133–3144. doi:10.1074/jbc.M109.077271

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Riehle C, Wende AR, Zaha VG, Pires KM, Wayment B, Olsen C, Bugger H, Buchanan J, Wang X, Moreira AB, Doenst T, Medina-Gomez G, Litwin SE, Lelliott CJ, Vidal-Puig A, Abel ED (2011) PGC-1beta deficiency accelerates the transition to heart failure in pressure overload hypertrophy. Circ Res 109:783–793. doi:10.1161/CIRCRESAHA.111.243964

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C (2008) Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol 382:790–801. doi:10.1016/j.jmb.2008.07.048

    Article  CAS  PubMed  Google Scholar 

  44. Shi T, Wang F, Stieren E, Tong Q (2005) SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 280:13560–13567. doi:10.1074/jbc.M414670200

    Article  CAS  PubMed  Google Scholar 

  45. Singh JP, Zhang K, Wu J, Yang X (2015) O-GlcNAc signaling in cancer metabolism and epigenetics. Cancer Lett 356:244–250. doi:10.1016/j.canlet.2014.04.014

    Article  CAS  PubMed  Google Scholar 

  46. Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129. doi:10.1152/physrev.00006.2004

    Article  CAS  PubMed  Google Scholar 

  47. Stepien G, Torroni A, Chung AB, Hodge JA, Wallace DC (1992) Differential expression of adenine nucleotide translocator isoforms in mammalian tissues and during muscle cell differentiation. J Biol Chem 267:14592–14597

    CAS  PubMed  Google Scholar 

  48. Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP (2009) Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest. 119:2758–2771. doi:10.1172/JCI39162

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Sundaresan NR, Samant SA, Pillai VB, Rajamohan SB, Gupta MP (2008) SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol 28:6384–6401. doi:10.1128/MCB.00426-08

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Taegtmeyer H (2002) Switching metabolic genes to build a better heart. Circulation 106:2043–2045. doi:10.1161/01.CIR.0000036760.42319.3F

    Article  PubMed  Google Scholar 

  51. Tanno M, Kuno A, Horio Y, Miura T (2012) Emerging beneficial roles of sirtuins in heart failure. Basic Res Cardiol 107:273. doi:10.1007/s00395-012-0273-5

    Article  PubMed Central  PubMed  Google Scholar 

  52. Tao R, Coleman MC, Pennington JD, Ozden O, Park SH, Jiang H, Kim HS, Flynn CR, Hill S, Hayes McDonald W, Olivier AK, Spitz DR, Gius D (2010) Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell 40:893–904. doi:10.1016/j.molcel.2010.12.013

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Tullio F, Angotti C, Perrelli MG, Penna C, Pagliaro P (2013) Redox balance and cardioprotection. Basic Res Cardiol 108:392. doi:10.1007/s00395-013-0392-7

    Article  PubMed  Google Scholar 

  54. Xiao CY, Chen M, Zsengeller Z, Li H, Kiss L, Kollai M, Szabo C (2005) Poly(ADP-Ribose) polymerase promotes cardiac remodeling, contractile failure, and translocation of apoptosis-inducing factor in a murine experimental model of aortic banding and heart failure. J Pharmacol Exp Ther 312:891–898. doi:10.1124/jpet.104.077164

    Article  CAS  PubMed  Google Scholar 

  55. Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, Liu CF, Grishin NV, Zhao Y (2009) Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Mol Cell Proteomics 8:215–225. doi:10.1074/mcp.M800187-MCP200

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327:1000–1004. doi:10.1126/science.1179689

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We like to thank the laboratory of E. Dale Abel for expert technical assistance in establishing the isolated working heart perfusion. This study was supported by a research grant of the Deutsche Forschungsgemeinschaft to H. B. (Bu2126/2-1).

Ethical standard

The manuscript does not contain clinical studies or patient data.

Author information

Authors and Affiliations

  1. Division of Cardiology and Angiology I, Heart Center Freiburg University, Hugstetter Str. 55, 79106, Freiburg, Germany

    Christoph Koentges, Katharina Pfeil, Rabea Dahlbock, Maria C. Cimolai, Maximilian Meyer-Steenbuck, Katarina Cenkerova, Michael M. Hoffmann, Katja E. Odening, Christoph Bode & Heiko Bugger

  2. Institute of Experimental and Clinical Pharmacology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany

    Tilman Schnick & Lutz Hein

  3. Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany

    Sebastian Wiese, Carsten Jaeger & Bernd Kammerer

  4. Institute for Clinical Chemistry and Laboratory Medicine, Freiburg University Hospital, Freiburg, Germany

    Michael M. Hoffmann

Authors
  1. Christoph Koentges
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katharina Pfeil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tilman Schnick
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sebastian Wiese
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rabea Dahlbock
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria C. Cimolai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maximilian Meyer-Steenbuck
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Katarina Cenkerova
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael M. Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carsten Jaeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Katja E. Odening
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Bernd Kammerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Lutz Hein
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Christoph Bode
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Heiko Bugger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heiko Bugger.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 483 kb)

Supplementary material 2 (PPT 8431 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koentges, C., Pfeil, K., Schnick, T. et al. SIRT3 deficiency impairs mitochondrial and contractile function in the heart. Basic Res Cardiol 110, 36 (2015). https://doi.org/10.1007/s00395-015-0493-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00395-015-0493-6

Keywords

Search

Navigation