Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4 and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications and ADP-ribosylation.

Extranuclear sirtuins and metabolic stress.:

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Extranuclear sirtuins and metabolic stress.

Antioxid Redox Signal. 2017 Jul 14;:

Authors: Elkhwanky MS, Hakkola J

Abstract

SIGNIFICANCE: Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4 and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications and ADP-ribosylation. Large-scale studies have revealed hundreds of target proteins regulated by different sirtuin modifications.

CRITICAL ISSUES: Sensing of the metabolic state and regulation of the sirtuin function and expression is a critical component of the machinery optimizing cellular functions in the switch from fed to fasting condition. Overfeeding, obesity and metabolic diseases cause metabolic stress that dysregulates the sirtuins which may play a role in the pathogenesis and complications of metabolic diseases such as type 2 diabetes, fatty liver disease and cardiac diseases. In the current review we will discuss the significance of the extranuclear sirtuins as metabolic regulators and in protection against the reactive oxygen species, and also how these sirtuins are regulated by metabolic status and their putative role in metabolic diseases.

FUTURE DIRECTIONS: To efficiently utilize sirtuins as drug targets for treatment of the metabolic diseases, better understanding of the sirtuin functions, targets, regulation and cross-talk is needed. Furthermore, more studies in humans are needed to confirm the many observations mainly made in animal and cell models so far.

PMID: 28707980 [PubMed - as supplied by publisher]

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