Review Volume 8, Issue 10 pp 2290—2307

The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis

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Figure 6E,F. Relationship of autophagy levels to vascular aging and atherosclerosis and the role of Sirt1 in the regulation of autophagy. (E) Sirt1 can form a molecular complex with several essential components of the autophagy machinery, including the autophagy-related genes (Atg) 5, Atg7 and Atg8. These autophagy components can be directly deacetylated by Sirt1. (F) Deacetylation of a nuclear pool of microtubule-associated protein light chain 3 (LC3) by Sirt1 initiates autophagy. Sirt1 deacetylates LC3 during starvation conditions. Deacetylated LC3 interacts with the nuclear protein DOR, and both proteins relocate from the nucleus to autophagosomes in the cytoplasm. Deacetylated LC3 interacts with Atg7 and other components of the ubiquitin-like conjugation machinery, leading to LC3 conjugation onto phosphatidylethanolamine (PE) and its incorporation into the early autophagosomal membrane.