Mitochondrial defect and PGC-1α dysfunction in parkin-associated familial Parkinson's disease

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1812, Issue 8, 2011, Pages 1041-1053

  Pacelli, Consiglia ^a   De Rasmo, Domenico ^a   Signorile, Anna ^a   Grattagliano, Ignazio ^a   di Tullio, Giuseppe ^b   D'Orazio, Andria ^b   Nico, Beatrice ^a   Comi, Giacomo Pietro ^c   Ronchi, Dario ^c   Ferranini, Ermanno ^e   Pirolo, Domenico ^e   Seibel, Peter ^d   Schubert, Susanna ^d   Gaballo, Antonio ^f   Villani, Gaetano ^a   Cocco, Tiziana ^a  

^a UNIVERSITY OF BARI   (Italy)

^b Consorzio Mario Negri Sud ^*  (Italy)

^c FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

^d Madonnina Hospital   (Italy)

^e UNIVERSITY OF LEIPZIG   (Germany)

^f CNR   (Italy)

Author keywords

Mitochondria; Oxidative stress; Parkin; Parkinson's disease; Peroxisome; PGC 1

Indexed keywords

PARKIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; REACTIVE OXYGEN METABOLITE;

ADULT; ARTICLE; BIOGENESIS; CASE REPORT; CELL ORGANELLE; DISEASE ASSOCIATION; DISORDERS OF PEROXISOMAL FUNCTIONS; ENERGY METABOLISM; FEMALE; GENE INDUCTION; GENE MUTATION; HETEROZYGOTE; HUMAN; HUMAN CELL; LIPID OXIDATION; MALE; MITOCHONDRIAL DNA DISORDER; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN DEPLETION;

ADULT; BASE SEQUENCE; DNA PRIMERS; ENERGY METABOLISM; FEMALE; FIBROBLASTS; HEAT-SHOCK PROTEINS; HUMANS; MALE; MITOCHONDRIA; MUTATION; OXIDATIVE STRESS; PARKINSON DISEASE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TRANSCRIPTION FACTORS; UBIQUITIN-PROTEIN LIGASES;

EID: 79958245892     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2010.12.022     Document Type: Article

References (87)

1. Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N., Johnson J., Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A., Marti-Masso J.F., Perez-Tur J., Wood N.W., Singleton A.B. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 2004, 44:595-600.
2. Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E.S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W.G., Lazzarini A.M., Duvoisin R.C., Di Iorio G., Golbe L.I., Nussbaum R.L. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997, 276:2045-2047.
3. Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998, 392:605-608.
4. Valente E.M., Abou-Sleiman P.M., Caputo V., Muqit M.M., Harvey K., Gispert S., Ali Z., Del Turco D., Bentivoglio A.R., Healy D.G., Albanese A., Nussbaum R., Gonzalez-Maldonado R., Deller T., Salvi S., Cortelli P., Gilks W.P., Latchman D.S., Harvey R.J., Dallapiccola B., Auburger G., Wood N.W. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004, 304:1158-1160.
5. Bonifati V., Rizzu P., Squitieri F., Krieger E., Vanacore N., van Swieten J.C., Brice A., van Duijn C.M., Oostra B., Meco G., Heutink P. DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol Sci 2003, 24:159-160.
6. Ramirez A., Heimbach A., Grundemann J., Stiller B., Hampshire D., Cid L.P., Goebel I., Mubaidin A.F., Wriekat A.L., Roeper J., Al-Din A., Hillmer A.M., Karsak M., Liss B., Woods C.G., Behrens M.I., Kubisch C. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 2006, 38:1184-1191.
7. Navarro A., Boveris A. Brain mitochondrial dysfunction and oxidative damage in Parkinson's disease. J Bioenerg Biomembr 2009, 41:517-521.
8. Zhu J., Chu C.T. Mitochondrial dysfunction in Parkinson's disease. J Alzheimers Dis 2010, 20(Suppl. 2):S325-S334.
9. Chinta S.J., Andersen J.K. Redox imbalance in Parkinson's disease. Biochim Biophys Acta 2008, 1780:1362-1367.
10. Zhou C., Huang Y., Przedborski S. Oxidative stress in Parkinson's disease: a mechanism of pathogenic and therapeutic significance. Ann NY Acad Sci 2008, 1147:93-104.
11. Graham D.G. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 1978, 14:633-643.
12. Kahle P.J., Haass C. How does parkin ligate ubiquitin to Parkinson's disease?. EMBO Rep 2004, 5:681-685.
13. Darios F., Corti O., Lucking C.B., Hampe C., Muriel M.P., Abbas N., Gu W.J., Hirsch E.C., Rooney T., Ruberg M., Brice A. Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet 2003, 12:517-526.
14. Palacino J.J., Sagi D., Goldberg M.S., Krauss S., Motz C., Wacker M., Klose J., Shen J. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 2004, 279:18614-18622.
15. Stichel C.C., Zhu X.R., Bader V., Linnartz B., Schmidt S., Lubbert H. Mono- and double-mutant mouse models of Parkinson's disease display severe mitochondrial damage. Hum Mol Genet 2007, 16:2377-2393.
16. Botella J.A., Bayersdorfer F., Gmeiner F., Schneuwly S. Modelling Parkinson's disease in Drosophila. Neuromolecular Med 2009, 11:268-280.
17. Greene J.C., Whitworth A.J., Kuo I., Andrews L.A., Feany M.B., Pallanck L.J. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA 2003, 100:4078-4083.
18. Muftuoglu M., Elibol B., Dalmizrak O., Ercan A., Kulaksiz G., Ogus H., Dalkara T., Ozer N. Mitochondrial complex I and IV activities in leukocytes from patients with parkin mutations. Mov Disord 2004, 19:544-548.
19. Winkler-Stuck K., Wiedemann F.R., Wallesch C.W., Kunz W.S. Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients. J Neurol Sci 2004, 220:41-48.
20. Mortiboys H., Thomas K.J., Koopman W.J., Klaffke S., Abou-Sleiman P., Olpin S., Wood N.W., Willems P.H., Smeitink J.A., Cookson M.R., Bandmann O. Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol 2008, 64:555-565.
21. Grunewald A., Voges L., Rakovic A., Kasten M., Vandebona H., Hemmelmann C., Lohmann K., Orolicki S., Ramirez A., Schapira A.H., Pramstaller P.P., Sue C.M., Klein C. Mutant Parkin impairs mitochondrial function and morphology in human fibroblasts. PLoS ONE 2010, 5:e12962.
22. Deng H., Dodson M.W., Huang H., Guo M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci USA 2008, 105:14503-14508.
23. Hochstrasser M. Origin and function of ubiquitin-like proteins. Nature 2009, 458:422-429.
24. Mukhopadhyay D., Riezman H. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 2007, 315:201-205.
25. Levine B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 2005, 120:159-162.
26. Narendra D., Tanaka A., Suen D.F., Youle R.J. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008, 183:795-803.
27. Whitworth A.J., Pallanck L.J. The PINK1/Parkin pathway: a mitochondrial quality control system?. J Bioenerg Biomembr 2009, 41:499-503.
28. Cherra S.J., Chu C.T. Autophagy in neuroprotection and neurodegeneration: a question of balance. Future Neurol 2008, 3:309-323.
29. Rothfuss O., Fischer H., Hasegawa T., Maisel M., Leitner P., Miesel F., Sharma M., Bornemann A., Berg D., Gasser T., Patenge N. Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair. Hum Mol Genet 2009, 18:3832-3850.
30. Puigserver P., Spiegelman B.M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003, 24:78-90.
31. St-Pierre J., Drori S., Uldry M., Silvaggi J.M., Rhee J., Jager S., Handschin C., Zheng K., Lin J., Yang W., Simon D.K., Bachoo R., Spiegelman B.M. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 2006, 127:397-408.
32. Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F., Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S., Breedveld G., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 2005, 365:412-415.
33. Dimri G.P., Lee X., Basile G., Acosta M., Scott G., Roskelley C., Medrano E.E., Linskens M., Rubelj I., Pereira-Smith O., et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 1995, 92:9363-9367.
34. Villani G., Attardi G. Polarographic assays of respiratory chain complex activity. Meth Cell Biol 2007, 80:121-133.
35. Greco M., Villani G., Mazzucchelli F., Bresolin N., Papa S., Attardi G. Marked aging-related decline in efficiency of oxidative phosphorylation in human skin fibroblasts. FASEB J 2003, 17:1706-1708.
36. Arnoldi A., Tonelli A., Crippa F., Villani G., Pacelli C., Sironi M., Pozzoli U., D'Angelo M.G., Meola G., Martinuzzi A., Crimella C., Redaelli F., Panzeri C., Renieri A., Comi G.P., Turconi A.C., Bresolin N., Bassi M.T. A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. Hum Mutat 2008, 29:522-531.
37. Villani G., Greco M., Papa S., Attardi G. Low reserve of cytochrome c oxidase capacity in vivo in the respiratory chain of a variety of human cell types. J Biol Chem 1998, 273:31829-31836.
38. Sgobbo P., Pacelli C., Grattagliano I., Villani G., Cocco T. Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2-mediated oxidative insult in H9C2 myocardial cells. Biochim Biophys Acta 2007, 1767:222-232.
39. Nochez Y., Arsene S., Gueguen N., Chevrollier A., Ferre M., Guillet V., Desquiret V., Toutain A., Bonneau D., Procaccio V., Amati-Bonneau P., Pisella P.J., Reynier P. Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect. Mol Vis 2009, 15:598-608.
40. Lund K.C., Peterson L.L., Wallace K.B. Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs. Antimicrob Agents Chemother 2007, 51:2531-2539.
41. Modica S., Morgano A., Salvatore L., Petruzzelli M., Vanier M.T., Valanzano R., Esposito D.L., Palasciano G., Duluc I., Freund J.N., Mariani-Costantini R., Moschetta A. Expression and localisation of insulin receptor substrate 2 in normal intestine and colorectal tumours. Regulation by intestine-specific transcription factor CDX2. Gut 2009, 58:1250-1259.
42. McLennan H.R., Degli Esposti M. The contribution of mitochondrial respiratory complexes to the production of reactive oxygen species. J Bioenerg Biomembr 2000, 32:153-162.
43. Cao Z., Li Y. Chemical induction of cellular antioxidants affords marked protection against oxidative injury in vascular smooth muscle cells. Biochem Biophys Res Commun 2002, 292:50-57.
44. Beauchamp C., Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem 1971, 44:276-287.
45. Levine R.L., Garland D., Oliver C.N., Amici A., Climent I., Lenz A.G., Ahn B.W., Shaltiel S., Stadtman E.R. Determination of carbonyl content in oxidatively modified proteins. Meth Enzymol 1990, 186:464-478.
46. Slater T.F., Sawyer B.C. The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reactions in rat liver fractions in vitro. General features of the systems used. Biochem J 1971, 123:805-814.
47. Schagger H., Link T.A., Engel W.D., von Jagow G. Isolation of the eleven protein subunits of the bc1 complex from beef heart. Meth Enzymol 1986, 126:224-237.
48. Nakaso K., Adachi Y., Yasui K., Sakuma K., Nakashima K. Detection of compound heterozygous deletions in the parkin gene of fibroblasts in patients with autosomal recessive hereditary parkinsonism. Neurosci Lett 2006, 400:44-47.
49. Robinson B.H., Petrova-Benedict R., Buncic J.R., Wallace D.C. Nonviability of cells with oxidative defects in galactose medium: a screening test for affected patient fibroblasts. Biochem Med Metab Biol 1992, 48:122-126.
50. Kelly D.P., Scarpulla R.C. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 2004, 18:357-368.
51. Lin J., Handschin C., Spiegelman B.M. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 2005, 1:361-370.
52. Lucking C.B., Durr A., Bonifati V., Vaughan J., De Michele G., Gasser T., Harhangi B.S., Meco G., Denefle P., Wood N.W., Agid Y., Brice A. Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med 2000, 342:1560-1567.
53. Aguiar Pde C., Lessa P.S., Godeiro C., Barsottini O., Felicio A.C., Borges V., Silva S.M., Saba R.A., Ferraz H.B., Moreira-Filho C.A., Andrade L.A. Genetic and environmental findings in early-onset Parkinson's disease Brazilian patients. Mov Disord 2008, 23:1228-1233.
54. Farrer M., Chan P., Chen R., Tan L., Lincoln S., Hernandez D., Forno L., Gwinn-Hardy K., Petrucelli L., Hussey J., Singleton A., Tanner C., Hardy J., Langston J.W. Lewy bodies and parkinsonism in families with parkin mutations. Ann Neurol 2001, 50:293-300.
55. Pramstaller P.P., Kis B., Eskelson C., Hedrich K., Scherer M., Schwinger E., Breakefield X.O., Kramer P.L., Ozelius L.J., Klein C. Phenotypic variability in a large kindred (Family LA) with deletions in the parkin gene. Mov Disord 2002, 17:424-426.
56. Lincoln S.J., Maraganore D.M., Lesnick T.G., Bounds R., de Andrade M., Bower J.H., Hardy J.A., Farrer M.J. Parkin variants in North American Parkinson's disease: cases and controls. Mov Disord 2003, 18:1306-1311.
57. Munhoz R.P., Sa D.S., Rogaeva E., Salehi-Rad S., Sato C., Medeiros H., Farrer M., Lang A.E. Clinical findings in a large family with a parkin ex3delta40 mutation. Arch Neurol 2004, 61:701-704.
58. Gautier C.A., Kitada T., Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci USA 2008, 105:11364-11369.
59. Kuroda Y., Mitsui T., Kunishige M., Shono M., Akaike M., Azuma H., Matsumoto T. Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 2006, 15:883-895.
60. Bowen B.C., Block R.E., Sanchez-Ramos J., Pattany P.M., Lampman D.A., Murdoch J.B., Quencer R.M. Proton MR spectroscopy of the brain in 14 patients with Parkinson disease. AJNR Am J Neuroradiol 1995, 16:61-68.
61. Dexter D.T., Carter C.J., Wells F.R., Javoy-Agid F., Agid Y., Lees A., Jenner P., Marsden C.D. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem 1989, 52:381-389.
62. Dalfo E., Portero-Otin M., Ayala V., Martinez A., Pamplona R., Ferrer I. Evidence of oxidative stress in the neocortex in incidental Lewy body disease. J Neuropathol Exp Neurol 2005, 64:816-830.
63. Castellani R.J., Perry G., Siedlak S.L., Nunomura A., Shimohama S., Zhang J., Montine T., Sayre L.M., Smith M.A. Hydroxynonenal adducts indicate a role for lipid peroxidation in neocortical and brainstem Lewy bodies in humans. Neurosci Lett 2002, 319:25-28.
64. Alam Z.I., Daniel S.E., Lees A.J., Marsden D.C., Jenner P., Halliwell B. A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. J Neurochem 1997, 69:1326-1329.
65. Floor E., Wetzel M.G. Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J Neurochem 1998, 70:268-275.
66. Ambani L.M., Van Woert M.H., Murphy S. Brain peroxidase and catalase in Parkinson disease. Arch Neurol 1975, 32:114-118.
67. Kish S.J., Morito C., Hornykiewicz O. Glutathione peroxidase activity in Parkinson's disease brain. Neurosci Lett 1985, 58:343-346.
68. Floyd R.A. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 1999, 222:236-245.
69. Camoes F., Bonekamp N.A., Delille H.K., Schrader M. Organelle dynamics and dysfunction: a closer link between peroxisomes and mitochondria. J Inherit Metab Dis 2009, 32:163-180.
70. Delille H.K., Alves R., Schrader M. Biogenesis of peroxisomes and mitochondria: linked by division. Histochem Cell Biol 2009, 131:441-446.
71. Bagattin A., Hugendubler L., Muelle E., Bagattin A., Hugendubler L., Mueller E. Transcriptional coactivator PGC-1{alpha} promotes peroxisomal remodeling and biogenesis. Proc Natl Acad Sci USA 2010, 107:20376-20381.
72. Koepke J.I., Nakrieko K.A., Wood C.S., Boucher K.K., Terlecky L.J., Walton P.A., Terlecky S.R. Restoration of peroxisomal catalase import in a model of human cellular aging. Traffic 2007, 8:1590-1600.
73. Koepke J.I., Wood C.S., Terlecky L.J., Walton P.A., Terlecky S.R. Progeric effects of catalase inactivation in human cells. Toxicol Appl Pharmacol 2008, 232:99-108.
74. Terlecky S.R., Koepke J.I., Walton P.A. Peroxisomes and aging. Biochim Biophys Acta 2006, 1763:1749-1754.
75. Narendra D.P., Jin S.M., Tanaka A., Suen D.F., Gautier C.A., Shen J., Cookson M.R., Youle R.J. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 2010, 8:e1000298.
76. Vives-Bauza C., Zhou C., Huang Y., Cui M., de Vries R.L., Kim J., May J., Tocilescu M.A., Liu W., Ko H.S., Magrane J., Moore D.J., Dawson V.L., Grailhe R., Dawson T.M., Li C., Tieu K., Przedborski S. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA 2010, 107:378-383.
77. Geisler S., Holmstrom K.M., Skujat D., Fiesel F.C., Rothfuss O.C., Kahle P.J., Springer W. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 2010, 12:119-131.
78. Lee J.Y., Nagano Y., Taylor J.P., Lim K.L., Yao T.P. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol 2010, 189:671-679.
79. Kim P.K., Hailey D.W., Mullen R.T., Lippincott-Schwartz J. Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci USA 2008, 105:20567-20574.
80. Chu C.T. A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease. Hum Mol Genet 2010, 19:R28-R37.
81. Cui L., Jeong H., Borovecki F., Parkhurst C.N., Tanese N., Krainc D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 2006, 127:59-69.
82. Chaturvedi R.K., Calingasan N.Y., Yang L., Hennessey T., Johri A., Beal M.F. Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington's disease following chronic energy deprivation. Hum Mol Genet 2010, 19:3190-3205.
83. Marmolino D., Manto M., Acquaviva F., Vergara P., Ravella A., Monticelli A., Pandolfo M. PGC-1alpha down-regulation affects the antioxidant response in Friedreich's ataxia. PLoS ONE 2010, 5:e10025.
84. Zheng B., Liao Z., Locascio J.J., Lesniak K.A., Roderick S.S., Watt M.L., Eklund A.C., Zhang-James Y., Kim P.D., Hauser M.A., Grunblatt E., Moran L.B., Mandel S.A., Riederer P., Miller R.M., Federoff H.J., Wullner U., Papapetropoulos S., Youdim M.B., Cantuti-Castelvetri I., Young A.B., Vance J.M., Davis R.L., Hedreen J.C., Adler C.H., Beach T.G., Graeber M.B., Middleton F.A., Rochet J.C., Scherzer C.R. PGC-1alpha, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med 2010, 2:52ra73.
85. Canto C., Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 2009, 20:98-105.
86. Aquilano K., Vigilanza P., Baldelli S., Pagliei B., Rotilio G., Ciriolo M.R. Peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) and sirtuin 1 (SIRT1) reside in mitochondria: possible direct function in mitochondrial biogenesis. J Biol Chem 2010, 285:21590-21599.
87. Lee I.H., Cao L., Mostoslavsky R., Lombard D.B., Liu J., Bruns N.E., Tsokos M., Alt F.W., Finkel T. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA 2008, 105:3374-3379.