SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation

In the citing paper

“Additionally, higher NAD+ levels can promote the deacetylase and deacylase activity of both nuclear SIRT1 and mitochondrial SIRT3, which regulate mitochondrial function and protect from high-fat diet-induced metabolic disease42,81,85–88.”

In the citing paper

“Sirt3 is an established deacetylase whose targets include long chain acyl CoA dehydrogenase (LCAD), succinate dehydrogenase and Mn superoxide dismutase (SOD2) (Hirschey et al., 2010; Qiu et al., 2010).”

In the citing paper

“Loss of SIRT3 has been shown to inhibit fatty acid oxidation ((Hirschey et al. 2010)); the same study showed decreased gluconeogenic production of glucose in response to cold challenge and decreased production of the ketone body beta-hydroxybutyrate during fasting.”

In the citing paper

“Loss of SIRT3 has been shown to inhibit fatty acid oxidation ((Hirschey et al. 2010)); the same study showed decreased gluconeogenic production of glucose in response to cold challenge and decreased production of the ketone body beta-hydroxybutyrate during fasting.”

In the citing paper

“SIRT3 is upregulated during fasting (Hirschey et al. 2010) and more generally by PGC-1α (Kong et al. 2010), which allows it to best control the hyperacetylation caused by acetyl-CoA-dependent metabolic processes such as fatty acid oxidation and ketone body metabolism.”

In the citing paper

“These mice also share other characteristics of human disorders of fatty acid oxidation, including cold intolerance and reduced basal ATP levels ((Hirschey et al. 2010)).”

In the citing paper

“SIRT3 promotes the efficient utilization of lipids as a primary source of acetyl-CoA during fasting by activating long-chain acyl-CoA dehydrogenase, a key enzyme in the β-oxidation of fatty acids, via deacetylation at K42 ((Hirschey et al. 2010)).”

In the citing paper

“Mice lacking SIRT3 accumulate β-oxidation precursors and intermediates, including triglycerides and long-chain fatty acids.”

In the citing paper

“In mice, SIRT3 is normally upregulated during fasting in liver and brown fat where it plays a role in fatty-acid oxidation by maintaining the deacetylation of long-chain acyl coenzyme A dehydrogenase in mitochondria (175).”

In the citing paper

“In its absence, SIRT3-deficient mice show reduced utilization of lipid stores during fasting: they have decreased fatty acid oxidation, accumulate triglycerides, and have diminished production of hepatic ATP.”

In the citing paper

“Upon fasting, SIRT3 expression is rapidly induced and deacetylates key residues on mitochondrial proteins (Hirschey et al, 2010).”

In the citing paper

“One week of HFD enhanced SIRT3 levels and prevented mitochondrial hyperacetylation despite the higher levels of lipid substrates (Hirschey et al, 2010).”

In the citing paper

“Dietary excess of lipids also dramatically changes mitochondrial protein acetylation.”

In the citing paper

“Conversely, prolonged HFD dramatically decreases SIRT3 expression, correlating with the appearance of mitochondrial hyperacetylation and mitochondrial dysfunction (Hirschey et al, 2010).”

In the citing paper

“For instance, acetylation of long-chain fatty acyl-CoA dehydrogenase, one of the four enzymes involved in the mitochondrial fat oxidation pathway, causes its inactivation, leading to fat accumulation [154], [155].”

In the citing paper

“SIRT3 has been reported to regulate mitochondrial fatty acid β-oxidation via deacetylation of long-chain acyl-CoA dehydrogenase, which, when dysregulated, results in defective fatty acid oxidation (Hirschey et al., 2010).”

In the citing paper

“which represents a key regulator of mitochondrial energy metabolism (Palacios et al., 2009; Hirschey et al., 2010, 2011; Anderson and Hirschey, 2012).”

In the citing paper

“Interestingly, SIRT3 is present in mitochondria, where it regulates the acetylation and activity of a variety of metabolic enzymes, suggesting additional ways that it might affect mitochondrial ROS production 73.”