Sirtuins and their influence on autophagy

Abstract

Sirtuins and autophagy are well-characterized agents that can promote longevity and protect individual organisms from age-associated diseases like neurodegenerative disorders. In recent years, more and more data has been obtained that discerned potential overlaps and crosstalk between Sirtuin proteins and autophagic activity. This review aims to summarize the advances within the field for each individual Sirtuin in mammalian systems. In brief, most Sirtuins have been implicated in promoting autophagy, with Sirtuin 1 and Sirtuin 6 showing the highest immediate involvement, while Sirtuin 4 and Sirtuin 5 only demonstrate occasional influence. The way Sirtuins regulate autophagy, however, is very diverse, as they have been shown to regulate gene expression of autophagy-associated genes and posttranslational modifications of proteins, with consequences for the activity and cellular localization of these proteins. They have also been shown to determine specific proteins for autophagic degradation. Overall, much data has been accumulated over recent years, yet many open questions remain. Especially although the dynamic between Sirtuin proteins and the immediate regulation of autophagic players like Light Chain 3B has been confirmed, many of these proteins have various orthologues in mammalian systems, and research so far has not exceeded the bona fide components of autophagy.

Keywords: HDAC; SIRT1; acetylation; autophagy; sirtuins.