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SirT1 is not required for exercise‐induced mitochondrial biogenesis, but maintains basal organelle content and function
Author(s) -
Menzies Keir Joe,
Singh Kaustabh,
Hood David A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1105.2
Subject(s) - mitochondrial biogenesis , mitochondrion , skeletal muscle , biogenesis , basal (medicine) , medicine , respiration , endocrinology , chemistry , biology , microbiology and biotechnology , biochemistry , anatomy , gene , insulin
The purpose of this research was to evaluate the role of SirT1 in exercise‐induced mitochondrial biogenesis. To do this, we produced skeletal‐muscle specific SirT1‐deficient (KO) mice. These KO mice had similar body, heart and muscle weights as wild‐type (WT) animals. Isolated muscle mitochondria from KO mice exhibited a 30% decline in COX activity, and 40% and 20% reductions in state 4 and state 3 respiration, respectively. There was a corresponding 2.5‐fold elevation in ROS generation during both state 4 and state 3 respiration. To examine the dependence of exercise‐induced mitochondrial biogenesis on SirT1, we trained the WT and KO mice on voluntary running wheels for 9 weeks. Both WT and KO mice ran the same average (14 km/day) and total distances. Voluntary exercise produced 1.4‐ and 1.7‐fold increases in COX activity in both the WT and KO animals, bringing them to the same absolute value of COX activity. In addition, the deficits in state 3 and 4 respiration, along with the elevated ROS levels in KO mice were rescued to values that were of the WT mice. Interestingly, Nampt protein, a positive modulator of SirT1 activity, increased by ~2.5‐fold in both WT and KO mice. These data indicate SirT1 is necessary for the maintenance of basal mitochondrial content and function. However, SirT1 does not does not seem to be necessary for exercise‐induced mitochondrial biogenesis.