Identifying an essential role of nuclear LC3 for autophagy

MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3), a mammalian ortholog of yeast Atg8, is a key protein contributing to major steps of autophagy. It has been recognized for a long time that LC3 is abundant in the nucleus despite the fact that it functions primarily in the cytoplasm where the autophagosomes and autolysosomes arise. An important question regarding nuclear LC3 is whether and how it participates in autophagy. In this punctum, we discuss our recent findings about the essential role for nuclear LC3 in starvation-induced autophagy. During nutrient-rich conditions, LC3 is distributed in an acetylated form in both the nucleus and cytoplasm. Nutrient deprivation promotes the redistribution of LC3 from the nucleus to the cytoplasm. This relocation depends on a deacetylation of the protein by the activated nuclear deacetylase SIRT1 and the association of the protein with its nuclear interaction partner TP53INP2/DOR. More importantly, the deacetylation is also required for LC3 to bind with ATG7 for its subsequent lipidation. Therefore, the results implicate the nuclear pool of LC3 as the primary source of membrane-conjugated LC3, and a regulation of deacetylation and nucleocytoplasmic translocation of LC3 in priming starved cells for autophagy induction.