Rabbit Anti-Human SIRT3 monoclonal antibody, clone L.940.2

Sirt3, as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolic adaption to various stresses. However, how to regulate Sirt3 activity responding to metabolic stress remains largely unknown. Here, we report Sirt3 as a SUMOylated protein in mitochondria. SUMOylation suppresses Sirt3 catalytic activity. SUMOylation-deficient Sirt3 shows elevated deacetylation on mitochondrial proteins and increased fatty acid oxidation. During fasting, SUMO-specific protease SENP1 is accumulated in mitochondria and quickly de-SUMOylates and activates Sirt3. SENP1 deficiency results in hyper-SUMOylation of Sirt3 and hyper-acetylation of mitochondrial proteins, which reduces mitochondrial metabolic adaption responding to fasting. Furthermore, we find that fasting induces SENP1 translocation into mitochondria to activate Sirt3. The studies on mice show that Sirt3 SUMOylation mutation reduces fat mass and antagonizes high-fat diet (HFD)-induced obesity via increasing oxidative phosphorylation and energy expenditure. Our results reveal that SENP1-Sirt3 signaling modulates Sirt3 activation and mitochondrial metabolism during metabolic stress.

Sirtuin3 (SIRT3), a NAD(+) dependent deacetylase, play a predominant role to control various metabolic processes involved in mammalian energy homeostasis. A study was conducted on two native goat breeds of Kerala, Malabari and Attappady Black, to analyze the tissue expression profile of caprine SIRT3, detect potential polymorphisms in exon 6 of SIRT3 and to study their association with production traits in goats. The mRNA isolated from ovary, uterus, liver and muscle of Malabari and Attappady Black goats were subjected to quantitative PCR (qPCR). Relative expression of caprine SIRT3 was significantly (p <= 0.05) higher in muscle, followed by uterus, liver and ovary. DNA was isolated from a total of 282 goats (176 Malabari and 106 Attappady Black) which exhibited three distinct banding patterns (PP, PQ and PR) for exon 6 fragment of SIRT3, on PCR-SSCP analysis. Sequencing the representative PCR products revealed the presence of two novel non-synonymous SNPs (c.802C > T and c.835 G > A) in the amplicon. The effect of the amino acid substitution on protein function was predicted by PolyPhen-2 tool which indicated that the amino acid change at position 802 was probably damaging and that at position 835 was benign. Further association analysis revealed that the diplotypes of exon 6 fragment had a significant (p <= 0.01) association with body weight. PR diplotpye was observed to be superior to PP and PQ diplotypes. All these results highlight the role of SIRT3 in growth traits and thus SIRT3 may be considered as a potential candidate gene for the production traits of goats.