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Michael N. Sack, M.D., Ph.D.


Principal Investigator thumbnail image

Michael N. Sack
Branch Chief

P: +1 301 402 9259
F: +1 301 402 0888

Full Publications Listing

Cyclophilin D Modulates the Mitochondrial Acetylome.
Nguyen TT, Wong RP, Menazza S, Sun J, Chen Y, Wang G, Gucek M, Steenbergen C, Sack MN, Murphy E.
Circ Res..
[Text Abstract on PubMed]

Mitochondrial metabolism, sirtuins, and aging.
Sack MN, Finkel T.
Cold Spring Harb Perspect Biol.;4(12).
[Text Abstract on PubMed]

The NAD-dependent deacetylase SIRT2 is required for programmed necrosis.
Narayan N, Lee IH, Borenstein R, Sun J, Wong R, Tong G, Fergusson MM, Liu J, Rovira II, Cheng HL, Wang G, Gucek M, Lombard D, Alt FW, Sack MN, Murphy E, Cao L, Finkel T.
Nature. 2012 Dec 13;492(7428):199-204.
[Text Abstract on PubMed]

Parkin in the regulation of fat uptake and mitochondrial biology: emerging links in the pathophysiology of Parkinson's disease.
Kim KY, Sack MN.
Curr. Opin. Lipidol. 2012 Jun;23(3):201-5.
[Text Abstract on PubMed]

Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1.
Scott I, Webster BR, Li JH, Sack MN.
Biochem. J. 2012 May 1;443(3):655-61.
[Text Abstract on PubMed]

Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins.
Avila C, Huang RJ, Stevens MV, Aponte AM, Tripodi D, Kim KY, Sack MN.
Exp. Clin. Endocrinol. Diabetes. 2012 Apr;120(4):248-51.
[Text Abstract on PubMed]

The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging.
Sack MN.
J. Mol. Cell. Cardiol. 2012 Mar;52(3):520-5.
[Text Abstract on PubMed]

The role of sirtuins in modulating redox stressors.
Webster BR, Lu Z, Sack MN, Scott I.
Free Radic. Biol. Med. 2012 Jan 15;52(2):281-90.
[Text Abstract on PubMed]

Mitochondrial metabolism, sirtuins, and aging.
Sack MN, Finkel T.
Cold Spring Harb Perspect Biol. 2012;4(12).
[Text Abstract on PubMed]

Mitofusin function is dependent on the distinct tissue and organ specific roles of mitochondria.
Sack MN.
J. Mol. Cell. Cardiol. 2011 Dec;51(6):881-2.
[Text Abstract on PubMed]

Emerging characterization of the role of SIRT3-mediated mitochondrial protein deacetylation in the heart.
Sack MN.
Am. J. Physiol. Heart Circ. Physiol. 2011 Dec;301(6):H2191-7.
[Text Abstract on PubMed]

Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore.
Nguyen TT, Stevens MV, Kohr M, Steenbergen C, Sack MN, Murphy E.
J. Biol. Chem. 2011 Nov 18;286(46):40184-92.
[Text Abstract on PubMed]

New horizons in cardioprotection: recommendations from the 2010 National Heart, Lung, and Blood Institute Workshop.
Schwartz Longacre L, Kloner RA, Arai AE, Baines CP, Bolli R, Braunwald E, Downey J, Gibbons RJ, Gottlieb RA, Heusch G, Jennings RB, Lefer DJ, Mentzer RM, Murphy E, Ovize M, Ping P, Przyklenk K, Sack MN, Vander Heide RS, Vinten-Johansen J, Yellon DM, National Heart, Lung, and Blood Institute, National Institutes of Health.
Circulation. 2011 Sep 6;124(10):1172-9.
[Text Abstract on PubMed]

Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells.
Kim KY, Stevens MV, Akter MH, Rusk SE, Huang RJ, Cohen A, Noguchi A, Springer D, Bocharov AV, Eggerman TL, Suen DF, Youle RJ, Amar M, Remaley AT, Sack MN.
J. Clin. Invest. 2011 Sep;121(9):3701-12.
[Text Abstract on PubMed]

PKCe promotes cardiac mitochondrial and metabolic adaptation to chronic hypobaric hypoxia by GSK3ß inhibition.
McCarthy J, Lochner A, Opie LH, Sack MN, Essop MF.
J. Cell. Physiol. 2011 Sep;226(9):2457-68.
[Text Abstract on PubMed]

The role of comorbidities in cardioprotection.
Sack MN, Murphy E.
J. Cardiovasc. Pharmacol. Ther. 2011 Sep-Dec;16(3-4):267-72.
[Text Abstract on PubMed]

SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity.
Lu Z, Bourdi M, Li JH, Aponte AM, Chen Y, Lombard DB, Gucek M, Pohl LR, Sack MN.
EMBO Rep. 2011 Aug;12(8):840-6.
[Text Abstract on PubMed]

Caloric excess or restriction mediated modulation of metabolic enzyme acetylation-proposed effects on cardiac growth and function.
Sack MN.
Biochim. Biophys. Acta. 2011 Jul;1813(7):1279-85.
[Text Abstract on PubMed]

Caloric restriction in leptin deficiency does not correct myocardial steatosis: failure to normalize PPAR{alpha}/PGC1{alpha} and thermogenic glycerolipid/fatty acid cycling.
Rame JE, Barouch LA, Sack MN, Lynn EG, Abu-Asab M, Tsokos M, Kern SJ, Barb JJ, Munson PJ, Halushka MK, Miller KL, Fox-Talbot K, Zhang J, Hare JM, Solomon MA, Danner RL.
Physiol. Genomics. 2011 Jun 28;43(12):726-38.
[Text Abstract on PubMed]

Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS).
Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM.
J. Exp. Med. 2011 Mar 14;208(3):519-33.
[Text Abstract on PubMed]

Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation.
Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, Watson PA, Birdsey N, Bao J, Gius D, Sack MN, Jing E, Kahn CR, Friedman JE, Jonscher KR.
Biochem. J. 2011 Feb 1;433(3):505-14.
[Text Abstract on PubMed]

Ambient oxygen promotes tumorigenesis.
Sung HJ, Ma W, Starost MF, Lago CU, Lim PK, Sack MN, Kang JG, Wang PY, Hwang PM.
PLoS ONE. 2011;6(5):e19785.
[Text Abstract on PubMed]

Wnt signaling regulates hepatic metabolism.
Liu H, Fergusson MM, Wu JJ, Rovira II, Liu J, Gavrilova O, Lu T, Bao J, Han D, Sack MN, Finkel T.
Sci Signal. 2011;4(158):ra6.
[Text Abstract on PubMed]

Rab4a signaling unmasks a pivotal link between myocardial homeostasis and metabolic remodeling in the diabetic heart.
Sack MN.
J. Mol. Cell. Cardiol. 2010 Dec;49(6):908-10.
[Text Abstract on PubMed]

TNFa protects cardiac mitochondria independently of its cell surface receptors.
Lacerda L, McCarthy J, Mungly SF, Lynn EG, Sack MN, Opie LH, Lecour S.
Basic Res. Cardiol. 2010 Nov;105(6):751-62.
[Text Abstract on PubMed]

Mitochondrial Fe-S cluster biogenesis, frataxin and the modulation of susceptibility to drug-induced cardiomyopathy.
Sack MN.
Aging (Albany NY). 2010 Nov;2(11):754-5.
[Text Abstract on PubMed]

SIRT3 is regulated by nutrient excess and modulates hepatic susceptibility to lipotoxicity.
Bao J, Scott I, Lu Z, Pang L, Dimond CC, Gius D, Sack MN.
Free Radic. Biol. Med. 2010 Oct 15;49(7):1230-7.
[Text Abstract on PubMed]

Transient upregulation of PGC-1alpha diminishes cardiac ischemia tolerance via upregulation of ANT1.
Lynn EG, Stevens MV, Wong RP, Carabenciov D, Jacobson J, Murphy E, Sack MN.
J. Mol. Cell. Cardiol. 2010 Oct;49(4):693-8.
[Text Abstract on PubMed]

Protein deacetylation by sirtuins: delineating a post-translational regulatory program responsive to nutrient and redox stressors.
Bao J, Sack MN.
Cell. Mol. Life Sci. 2010 Sep;67(18):3073-87.
[Text Abstract on PubMed]

Characterization of the murine SIRT3 mitochondrial localization sequence and comparison of mitochondrial enrichment and deacetylase activity of long and short SIRT3 isoforms.
Bao J, Lu Z, Joseph JJ, Carabenciov D, Dimond CC, Pang L, Samsel L, McCoy, Leclerc J, Nguyen P, Gius D, Sack MN.
J. Cell. Biochem. 2010 May;110(1):238-47.
[Text Abstract on PubMed]

The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance.
Pagel-Langenickel I, Bao J, Pang L, Sack MN.
Endocr. Rev. 2010 Feb;31(1):25-51.
[Text Abstract on PubMed]

The emerging characterization of lysine residue deacetylation on the modulation of mitochondrial function and cardiovascular biology.
Lu Z, Scott I, Webster BR, Sack MN.
Circ. Res. 2009 Oct 23;105(9):830-41.
[Text Abstract on PubMed]

Type 2 diabetes, mitochondrial biology and the heart.
Sack MN.
J. Mol. Cell. Cardiol. 2009 Jun;46(6):842-9.
[Text Abstract on PubMed]

Innate short-circuiting of mitochondrial metabolism in cardiac hypertrophy: identification of novel consequences of enhanced anaplerosis.
Sack MN.
Circ. Res. 2009 Mar 27;104(6):717-9.
[Text Abstract on PubMed]

The regulation and control of mitochondrial homeostasis in changing cardiac tolerance to ischemia-reperfusion injury: a focused issue.
Sack MN, Murphy E, Schulz R.
Basic Res. Cardiol. 2009 Mar;104(2):111-2.
[Text Abstract on PubMed]

Signal transducer and activator of transcription 3 is involved in the cardioprotective signalling pathway activated by insulin therapy at reperfusion.
Fuglesteg BN, Suleman N, Tiron C, Kanhema T, Lacerda L, Andreasen TV, Sack MN, Jonassen AK, Mjøs OD, Opie LH, Lecour S.
Basic Res. Cardiol. 2008 Sep;103(5):444-53.
[Text Abstract on PubMed]

ATF-1 is a hypoxia-responsive transcriptional activator of skeletal muscle mitochondrial-uncoupling protein 3.
Lu Z, Sack MN.
J. Biol. Chem. 2008 Aug 22;283(34):23410-8.
[Text Abstract on PubMed]

SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells.
Lynn EG, McLeod CJ, Gordon JP, Bao J, Sack MN.
FEBS Lett. 2008 Aug 20;582(19):2857-62.
[Text Abstract on PubMed]

PGC-1alpha integrates insulin signaling, mitochondrial regulation, and bioenergetic function in skeletal muscle.
Pagel-Langenickel I, Bao J, Joseph JJ, Schwartz DR, Mantell BS, Xu X, Raghavachari N, Sack MN.
J. Biol. Chem. 2008 Aug 15;283(33):22464-72.
[Text Abstract on PubMed]

Targeting the mitochondria to augment myocardial protection.
Schwartz DR, Sack MN.
Curr Opin Pharmacol. 2008 Apr;8(2):160-5.
[Text Abstract on PubMed]

A discordance in rosiglitazone mediated insulin sensitization and skeletal muscle mitochondrial content/activity in Type 2 diabetes mellitus.
Pagel-Langenickel I, Schwartz DR, Arena RA, Minerbi DC, Johnson DT, Waclawiw MA, Cannon, Balaban RS, Tripodi DJ, Sack MN.
Am. J. Physiol. Heart Circ. Physiol. 2007 Nov;293(5):H2659-66.
[Text Abstract on PubMed]

Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide.
True AL, Olive M, Boehm M, San H, Westrick RJ, Raghavachari N, Xu X, Lynn EG, Sack MN, Munson PJ, Gladwin MT, Nabel EG.
Circ. Res. 2007 Oct 26;101(9):893-901.
[Text Abstract on PubMed]

Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer.
Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, Wang X, MacArthur PH, Shoja A, Raghavachari N, Calvert JW, Brookes PS, Lefer DJ, Gladwin MT.
J. Exp. Med. 2007 Sep 3;204(9):2089-102.
[Text Abstract on PubMed]

The regulation, control, and consequences of mitochondrial oxygen utilization and disposition in the heart and skeletal muscle during hypoxia.
Lynn EG, Lu Z, Minerbi D, Sack MN.
Antioxid. Redox Signal. 2007 Sep;9(9):1353-61.
[Text Abstract on PubMed]

Diazoxide-induced respiratory inhibition - a putative mitochondrial K(ATP) channel independent mechanism of pharmacological preconditioning.
Minners J, Lacerda L, Yellon DM, Opie LH, McLeod CJ, Sack MN.
Mol. Cell. Biochem. 2007 Jan;294(1-2):11-8.
[Text Abstract on PubMed]

Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance.
Sack MN.
Cardiovasc. Res. 2006 Nov 1;72(2):210-9.
[Text Abstract on PubMed]

Exploring mitochondria in the intact ischemic heart: advancing technologies to image intracellular function.
Sack MN.
Circulation. 2006 Oct 3;114(14):1452-4.
[Text Abstract on PubMed]

Ceramide attenuates hypoxic cell death via reactive oxygen species signaling.
Lecour S, Van der Merwe E, Opie LH, Sack MN.
J. Cardiovasc. Pharmacol. 2006 Jan;47(1):158-63.
[Text Abstract on PubMed]

Uncoupling proteins 2 and 3 function in concert to augment tolerance to cardiac ischemia.
McLeod CJ, Aziz A, Hoyt, McCoy, Sack MN.
J. Biol. Chem. 2005 Sep 30;280(39):33470-6.
[Text Abstract on PubMed]

H-89, a non-specific inhibitor of protein kinase A, promotes post-ischemic cardiac contractile recovery and reduces infarct size.
Makaula S, Lochner A, Genade S, Sack MN, Awan MM, Opie LH.
J. Cardiovasc. Pharmacol. 2005 Apr;45(4):341-7.
[Text Abstract on PubMed]

PKCepsilon activation augments cardiac mitochondrial respiratory post-anoxic reserve--a putative mechanism in PKCepsilon cardioprotection.
McCarthy J, McLeod CJ, Minners J, Essop MF, Ping P, Sack MN.
J. Mol. Cell. Cardiol. 2005 Apr;38(4):697-700.
[Text Abstract on PubMed]

The mitochondrial biogenesis regulatory program in cardiac adaptation to ischemia--a putative target for therapeutic intervention.
McLeod CJ, Pagel I, Sack MN.
Trends Cardiovasc. Med. 2005 Apr;15(3):118-23.
[Text Abstract on PubMed]

Genetic depletion of cardiac myocyte STAT-3 abolishes classical preconditioning.
Smith RM, Suleman N, Lacerda L, Opie LH, Akira S, Chien KR, Sack MN.
Cardiovasc. Res. 2004 Sep 1;63(4):611-6.
[Text Abstract on PubMed]

Delayed ischemic preconditioning activates nuclear-encoded electron-transfer-chain gene expression in parallel with enhanced postanoxic mitochondrial respiratory recovery.
McLeod CJ, Jeyabalan AP, Minners JO, Clevenger R, Hoyt, Sack MN.
Circulation. 2004 Aug 3;110(5):534-9.
[Text Abstract on PubMed]

p70s6 kinase is a functional target of insulin activated Akt cell-survival signaling.
Jonassen AK, Mjøs OD, Sack MN.
Biochem. Biophys. Res. Commun. 2004 Feb 27;315(1):160-5.
[Text Abstract on PubMed]

Hypoxia-induced decrease of UCP3 gene expression in rat heart parallels metabolic gene switching but fails to affect mitochondrial respiratory coupling.
Essop MF, Razeghi P, McLeod C, Young ME, Taegtmeyer H, Sack MN.
Biochem. Biophys. Res. Commun. 2004 Feb 6;314(2):561-4.
[Text Abstract on PubMed]

[Sphingolipid signaling: a potential pathway for TNF-alpha induced preconditioning].
Lecour S, Sack MN, Opie LH.
Ann Cardiol Angeiol (Paris). 2003 Dec;52(6):363-9.
[Text Abstract on PubMed]

Counter-regulatory effects of incremental hypoxia on the transcription of a cardiac fatty acid oxidation enzyme-encoding gene.
Ngumbela KC, Sack MN, Essop MF.
Mol. Cell. Biochem. 2003 Aug;250(1-2):151-8.
[Text Abstract on PubMed]

Mitochondrial plasticity in classical ischemic preconditioning-moving beyond the mitochondrial KATP channel.
Minners J, McLeod CJ, Sack MN.
Cardiovasc. Res. 2003 Jul 1;59(1):1-6.
[Text Abstract on PubMed]

Insulin therapy as an adjunct to reperfusion after acute coronary ischemia: a proposed direct myocardial cell survival effect independent of metabolic modulation.
Sack MN, Yellon DM.
J. Am. Coll. Cardiol. 2003 Apr 16;41(8):1404-7.
[Text Abstract on PubMed]

Metabolic plasticity and the promotion of cardiac protection in ischemia and ischemic preconditioning.
Opie LH, Sack MN.
J. Mol. Cell. Cardiol. 2002 Sep;34(9):1077-89.
[Text Abstract on PubMed]

Innate immunity and cardiac preconditioning: a putative intrinsic cardioprotective program.
Smith RM, Lecour S, Sack MN.
Cardiovasc. Res. 2002 Aug 15;55(3):474-82.
[Text Abstract on PubMed]

Identification of a novel role for sphingolipid signaling in TNF alpha and ischemic preconditioning mediated cardioprotection.
Lecour S, Smith RM, Woodward B, Opie LH, Rochette L, Sack MN.
J. Mol. Cell. Cardiol. 2002 May;34(5):509-18.
[Text Abstract on PubMed]

Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling.
Jonassen AK, Sack MN, Mjøs OD, Yellon DM.
Circ. Res. 2001 Dec 7;89(12):1191-8.
[Text Abstract on PubMed]

Ischemic and pharmacological preconditioning in Girardi cells and C2C12 myotubes induce mitochondrial uncoupling.
Minners J, Lacerda L, McCarthy J, Meiring JJ, Yellon DM, Sack MN.
Circ. Res. 2001 Oct 26;89(9):787-92.
[Text Abstract on PubMed]

Enhanced angiotensin II activity in heart failure: reevaluation of the counterregulatory hypothesis of receptor subtypes.
Opie LH, Sack MN.
Circ. Res. 2001 Apr 13;88(7):654-8.
[Text Abstract on PubMed]

TNF alpha is required for hypoxia-mediated right ventricular hypertrophy.
Smith RM, McCarthy J, Sack MN.
Mol. Cell. Biochem. 2001 Mar;219(1-2):139-43.
[Text Abstract on PubMed]

Delta opioid receptor stimulation mimics ischemic preconditioning in human heart muscle.
Bell SP, Sack MN, Patel A, Opie LH, Yellon DM.
J. Am. Coll. Cardiol. 2000 Dec;36(7):2296-302.
[Text Abstract on PubMed]

Mechanisms whereby glucose deprivation triggers metabolic preconditioning in the isolated rat heart.
Awan MM, Makaula S, Forresti S, Sack MN, Opie LH.
Mol. Cell. Biochem. 2000 Aug;211(1-2):111-21.
[Text Abstract on PubMed]

Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection.
Minners J, van den Bos EJ, Yellon DM, Schwalb H, Opie LH, Sack MN.
Cardiovasc. Res. 2000 Jul;47(1):68-73.
[Text Abstract on PubMed]

Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism.
Jonassen AK, Brar BK, Mjøs OD, Sack MN, Latchman DS, Yellon DM.
J. Mol. Cell. Cardiol. 2000 May;32(5):757-64.
[Text Abstract on PubMed]

Tumor necrosis factor in myocardial hypertrophy and ischaemia--an anti-apoptotic perspective.
Sack MN, Smith RM, Opie LH.
Cardiovasc. Res. 2000 Feb;45(3):688-95.
[Text Abstract on PubMed]

Coordinate regulation of metabolic enzyme encoding genes during cardiac development and following carvedilol therapy in spontaneously hypertensive rats.
Sack MN, Harrington LS, Jonassen AK, Mjøs OD, Yellon DM.
Cardiovasc Drugs Ther. 2000 Feb;14(1):31-9.
[Text Abstract on PubMed]

The energy substrate switch during development of heart failure: gene regulatory mechanisms (Review).
Sack MN, Kelly DP.
Int. J. Mol. Med. 1998 Jan;1(1):17-24.
[Text Abstract on PubMed]

A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program.
Sack MN, Disch DL, Rockman HA, Kelly DP.
Proc. Natl. Acad. Sci. U.S.A. 1997 Jun 10;94(12):6438-43.
[Text Abstract on PubMed]

Fatty acid oxidation enzyme gene expression is downregulated in the failing heart.
Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP.
Circulation. 1996 Dec 1;94(11):2837-42.
[Text Abstract on PubMed]

Autoantibody titers to oxidized low-density lipoprotein in patients with coronary atherosclerosis.
Bui MN, Sack MN, Moutsatsos G, Lu DY, Katz P, McCown R, Breall JA, Rackley CE.
Am. Heart J. 1996 Apr;131(4):663-7.
[Text Abstract on PubMed]

Effect of antioxidant vitamins on low density lipoprotein oxidation and impaired endothelium-dependent vasodilation in patients with hypercholesterolemia.
Gilligan DM, Sack MN, Guetta V, Casino PR, Quyyumi AA, Rader DJ, Panza JA, Cannon.
J. Am. Coll. Cardiol. 1994 Dec;24(7):1611-7.
[Text Abstract on PubMed]

Restriction isotyping of apoprotein E.
Sack MN, Hoeg JM.
Ann. Intern. Med. 1994 Nov 15;121(10):816.
[Text Abstract on PubMed]

Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women.
Sack MN, Rader DJ, Cannon.
Lancet. 1994 Jan 29;343(8892):269-70.
[Text Abstract on PubMed]