Emerging Roles of SIRT3 in Cardiac Metabolism

Abstract

The heart is a highly metabolically active organ that predominantly utilizes fatty acids as an energy substrate. The heart also derives some part of its energy by oxidation of other substrates, including glucose, lactose, amino acids and ketones. The critical feature of cardiac pathology is metabolic remodeling and loss of metabolic flexibility. Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins (SIRT1 to SIRT7), with NAD+ dependent deacetylase activity. SIRT3 is expressed in high levels in healthy hearts but downregulated in the aged or diseased hearts. Experimental evidence shows that increasing SIRT3 levels or activity can ameliorate several cardiac pathologies. The primary deacetylation targets of SIRT3 are mitochondrial proteins, most of which are involved in energy metabolism. Thus, SIRT3 improves cardiac health by modulating cardiac energetics. In this review, we discuss the essential role of SIRT3 in regulating cardiac metabolism in the context of physiology and pathology. Specifically, we summarize the recent advancements that emphasize the critical role of SIRT3 as a master regulator of cardiac metabolism. We also present a comprehensive view of all known activators of SIRT3, and elaborate on their therapeutic potential to ameliorate energetic abnormalities in various cardiac pathologies.

Deficient mitochondrial respiration impairs sirtuin activity in dorsal root ganglia in Friedreich Ataxia mouse and cell models

“…Accordingly, as an NAD + -dependent enzyme, mitochondrial SirT3 activity is expected to decrease in both models. The role of SirT3 in cardiac metabolism has been well described [19] [46] In the context of FA, SirT3 has been studied in two conditional mouse models that develop a fatal cardiomyopathy and impaired activity in respiratory complexes [40]. They showed marked hyperacetylation of cardiac mitochondrial proteins and a huge decrease (85-fold) in the NAD + /NADH ratio.…”

Pyrroloquinoline Quinone (PQQ): a novel approach to managing chronic inflammatory response syndrome and mitochondrial dysfunction

“…Sirtuin 3 increases can improve heart pathologies, according to research. 33 Sirtuin 3 mostly deacetylates mitochondrial proteins involved in energy production. Sirtuin 3 regulates cardiac energetics, improving cardiac heath.…”

Metabolic reprogramming: A novel therapeutic target in diabetic kidney disease

“…SIRT3, belonging to the sirtuin family, is a highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase (de Oliveira et al, 2010). It is expressed at high levels in the kidneys (Jin et al, 2009) as long or short isoforms (Murugasamy et al, 2022). The short isoform is predominant in the mitochondrial matrix, where it acts as a functionally active mitochondrial deacetylase (Onyango et al, 2002;Schwer et al, 2002).…”