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.

Sirtuin 1 activator alleviated lethal inflammatory injury via promotion of autophagic degradation of pyruvate kinase M2

“…Autophagy is regulated by PTMs such as acetylation ( Xu and Wan, 2022 ), and SIRT1 is a representative deacetylase that profoundly involved in the regulation of autophagy ( Baeken, 2023 ). Previous studies have revealed that SIRT1 modulates autophagy at transcriptional level via deacetylating Forkhead Box O1 (FOXO1) and Forkhead Box O3 (FOXO3) ( Hariharan et al, 2010 ; Dusabimana et al, 2019 ).…”

“…Sirtuin 1 (SIRT1), a longevity factor, is a well-studied deacetylase that removes acetyl group from the lysine residue from acetylated proteins ( Yang et al, 2022 ). Previous studies have found that SIRT1 functions as a crucial regulator at different stages of autophagy and activation of SIRT1 promoted autophagy ( Baeken, 2023 ). In addition, treatment with SIRT1 activator has been suggested as an effective approach to alleviate inflammatory injury ( Yang et al, 2022 ).…”

Narrative review of ferroptosis in obesity

“…60 SIRT1 is a nicotinamide adenine dinucleotide-dependent histone deacetylase, promote longevity and protect individual organisms from age-associated diseases. 61 In additional, sphingosine 1-phosphate (S1P) alleviates radiation-induced ferroptosis in ovarian granulosa cells by upregulating GPX4. Physical activity activates the SIRT1 pathway, 62 which has also been linked to creativity.…”

In vitro methods in autophagy research: Applications in neurodegenerative diseases and mood disorders

“…In compromised neurons, autophagy vacuoles containing AB pack into large structures forming flower-like perikaryal rosettes known as PANTHOS (poisonous Anthos or flower) which occur in the brains of AD patients ( Lee et al, 2022 ). Another key player in autolysosome acidification is SIRT5, a sirtuin protein found in the mitochondria ( Baeken, 2023 ). SIRT5 mediates the deacetylation and activation of the enzyme lactate dehydrogenase B found on the lysosomal membrane supplying the lysosomes with protons for lysosomal acidification ( Baeken, 2023 ).…”

“…Another key player in autolysosome acidification is SIRT5, a sirtuin protein found in the mitochondria ( Baeken, 2023 ). SIRT5 mediates the deacetylation and activation of the enzyme lactate dehydrogenase B found on the lysosomal membrane supplying the lysosomes with protons for lysosomal acidification ( Baeken, 2023 ). Due to both its role in lysosomal acidification and its decreased expression in AD, SIRT5 has been regarded as an attractive autophagy-related target in AD therapeutics ( Baeken, 2023 ).…”