Coumestrol
Induces Mitochondrial Biogenesis by Activating
Sirt1 in Cultured Skeletal Muscle Cells
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Abstract
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<sup>+</sup>/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