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Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise.
J Biol Chem 2011; 286(35):30561-70JB

Abstract

The protein deacetylase, sirtuin 1 (SIRT1), is a proposed master regulator of exercise-induced mitochondrial biogenesis in skeletal muscle, primarily via its ability to deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). To investigate regulation of mitochondrial biogenesis by SIRT1 in vivo, we generated mice lacking SIRT1 deacetylase activity in skeletal muscle (mKO). We hypothesized that deacetylation of PGC-1α and mitochondrial biogenesis in sedentary mice and after endurance exercise would be impaired in mKO mice. Skeletal muscle contractile characteristics were determined in extensor digitorum longus muscle ex vivo. Mitochondrial biogenesis was assessed after 20 days of voluntary wheel running by measuring electron transport chain protein content, enzyme activity, and mitochondrial DNA expression. PGC-1α expression, nuclear localization, acetylation, and interacting protein association were determined following an acute bout of treadmill exercise (AEX) using co-immunoprecipitation and immunoblotting. Contrary to our hypothesis, skeletal muscle endurance, electron transport chain activity, and voluntary wheel running-induced mitochondrial biogenesis were not impaired in mKO versus wild-type (WT) mice. Moreover, PGC-1α expression, nuclear translocation, activity, and deacetylation after AEX were similar in mKO versus WT mice. Alternatively, we made the novel observation that deacetylation of PGC-1α after AEX occurs in parallel with reduced nuclear abundance of the acetyltransferase, general control of amino-acid synthesis 5 (GCN5), as well as reduced association between GCN5 and nuclear PGC-1α. These findings demonstrate that SIRT1 deacetylase activity is not required for exercise-induced deacetylation of PGC-1α or mitochondrial biogenesis in skeletal muscle and suggest that changes in GCN5 acetyltransferase activity may be an important regulator of PGC-1α activity after exercise.

Authors+Show Affiliations

Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California 95616, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21757760

Citation

Philp, Andrew, et al. "Sirtuin 1 (SIRT1) Deacetylase Activity Is Not Required for Mitochondrial Biogenesis or Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha (PGC-1alpha) Deacetylation Following Endurance Exercise." The Journal of Biological Chemistry, vol. 286, no. 35, 2011, pp. 30561-70.
Philp A, Chen A, Lan D, et al. Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise. J Biol Chem. 2011;286(35):30561-70.
Philp, A., Chen, A., Lan, D., Meyer, G. A., Murphy, A. N., Knapp, A. E., ... Schenk, S. (2011). Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise. The Journal of Biological Chemistry, 286(35), pp. 30561-70. doi:10.1074/jbc.M111.261685.
Philp A, et al. Sirtuin 1 (SIRT1) Deacetylase Activity Is Not Required for Mitochondrial Biogenesis or Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha (PGC-1alpha) Deacetylation Following Endurance Exercise. J Biol Chem. 2011 Sep 2;286(35):30561-70. PubMed PMID: 21757760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise. AU - Philp,Andrew, AU - Chen,Ai, AU - Lan,Debin, AU - Meyer,Gretchen A, AU - Murphy,Anne N, AU - Knapp,Amy E, AU - Olfert,I Mark, AU - McCurdy,Carrie E, AU - Marcotte,George R, AU - Hogan,Michael C, AU - Baar,Keith, AU - Schenk,Simon, Y1 - 2011/07/11/ PY - 2011/7/16/entrez PY - 2011/7/16/pubmed PY - 2011/10/26/medline SP - 30561 EP - 70 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 286 IS - 35 N2 - The protein deacetylase, sirtuin 1 (SIRT1), is a proposed master regulator of exercise-induced mitochondrial biogenesis in skeletal muscle, primarily via its ability to deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). To investigate regulation of mitochondrial biogenesis by SIRT1 in vivo, we generated mice lacking SIRT1 deacetylase activity in skeletal muscle (mKO). We hypothesized that deacetylation of PGC-1α and mitochondrial biogenesis in sedentary mice and after endurance exercise would be impaired in mKO mice. Skeletal muscle contractile characteristics were determined in extensor digitorum longus muscle ex vivo. Mitochondrial biogenesis was assessed after 20 days of voluntary wheel running by measuring electron transport chain protein content, enzyme activity, and mitochondrial DNA expression. PGC-1α expression, nuclear localization, acetylation, and interacting protein association were determined following an acute bout of treadmill exercise (AEX) using co-immunoprecipitation and immunoblotting. Contrary to our hypothesis, skeletal muscle endurance, electron transport chain activity, and voluntary wheel running-induced mitochondrial biogenesis were not impaired in mKO versus wild-type (WT) mice. Moreover, PGC-1α expression, nuclear translocation, activity, and deacetylation after AEX were similar in mKO versus WT mice. Alternatively, we made the novel observation that deacetylation of PGC-1α after AEX occurs in parallel with reduced nuclear abundance of the acetyltransferase, general control of amino-acid synthesis 5 (GCN5), as well as reduced association between GCN5 and nuclear PGC-1α. These findings demonstrate that SIRT1 deacetylase activity is not required for exercise-induced deacetylation of PGC-1α or mitochondrial biogenesis in skeletal muscle and suggest that changes in GCN5 acetyltransferase activity may be an important regulator of PGC-1α activity after exercise. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/21757760/Sirtuin_1__SIRT1__deacetylase_activity_is_not_required_for_mitochondrial_biogenesis_or_peroxisome_proliferator_activated_receptor_gamma_coactivator_1alpha__PGC_1alpha__deacetylation_following_endurance_exercise_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=21757760 DB - PRIME DP - Unbound Medicine ER -