Abstract

Sirtuins are the endogenously present anti-aging protein deacetylases that regulate the mitochondrial biogenesis and function. Especially Sirt3, a mitochondrial sirtuin, is well known for maintaining mitochondrial function and health. In the present study, we have explored the novel role of Sirt3 in mitochondrial biogenesis and shown the role of Sirt3 in mito-nuclear communication through AMPK-α in Sirt3 knockdown and Sirt3 overexpressed H9c2 cells. The study found that impaired mitochondrial function in Sirt3-knockdown H9c2 cells was associated with decreased expression of mitochondrial DNA encoded genes, reduced SOD2 expression and activity. The study also revealed that Sirt3 knockdown affects mitochondrial biogenesis and dynamics. To further confirm the role of Sirt3 on mitochondrial biogenesis and health, we did Sirt3 overexpression in H9c2 cells. Sirt3 overexpression enhanced the expression of mitochondrial DNA encoded genes, increased SOD2 activity and altered mitochondrial dynamics. Sirt3 overexpression also caused an increase in mitochondrial biogenesis gene and protein (PGC-1α and TFAM) expression. All these changes were confirmed with mitochondrial functional parameters like basal respiration, maximal respiratory capacity, spare respiratory capacity and ATP production. We found decreased mitochondrial function in Sirt3-knockdown H9c2 cells when compared to control H9c2 cells. Together our data conclude that Sirt3 regulates cardiac mitochondrial health and function through the Sirt3-AMPKα-PGC-1α axis.

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