Coumestrol induces mitochondrial biogenesis by activating Sirt1 in cultured skeletal muscle cells.
The mitochondrion is a central organelle in cellular energy homeostasis; thus, reduced mitochondrial activity has been associated with aging and metabolic disorders. This paper provides biological evidence that coumestrol, which is a natural isoflavone, activates mitochondrial biogenesis. In cultured myocytes, coumestrol activated the silent information regulator two ortholog 1 (Sirt1) through the elevation of the intracellular NAD(+)/NADH ratio. Coumestrol also increased the mitochondrial contents and induced the expression of key proteins in the mitochondrial electron transfer chain in cultured myocytes. A Sirt1 inhibitor and Sirt1-targeting siRNAs abolished the effect of coumestrol on mitochondrial biogenesis. Similar to an increase in mitochondrial content, coumestrol improved myocyte function with increased ATP concentration. Taken together, the data suggest that coumestrol is a novel inducer of mitochondrial biogenesis through the activation of Sirt1.
College of Life and Environmental Sciences, Division of Food Science, Korea University , Seoul 136-713, Republic of Korea.
Dae-Bang
DB
Seo
Hyun Woo
HW
Jeong
Sang-Jun
SJ
Lee
Sung-Joon
SJ
Lee
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003375:Coumestrol / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D032342:Muscle Cells / Q000187:drug effects* / Q000201:enzymology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
D000255:Adenosine Triphosphate; D056564:Sirtuin 1; D003375:Coumestrol