LC3B-II deacetylation by histone deacetylase 6 is involved in serum-starvation-induced autophagic degradation.
Autophagy is a conserved mechanism for controlling the degradation of misfolded proteins and damaged organelles in eukaryotes and can be induced by nutrient withdrawal, including serum starvation. Although differential acetylation of autophagy-related proteins has been reported to be involved in autophagic flux, the regulation of acetylated microtubule-associated protein 1 light chain 3 (LC3) is incompletely understood. In this study, we found that the acetylation levels of phosphotidylethanolamine (PE)-conjugated LC3B (LC3B-II), which is a critical component of double-membrane autophagosome, were profoundly decreased in HeLa cells upon autophagy induction by serum starvation. Pretreatment with lysosomal inhibitor chloroquine did not attenuate such deacetylation. Under normal culture medium, we observed increased levels of acetylated LC3B-II in cells treated with tubacin, a specific inhibitor of histone deacetylase 6 (HDAC6). However, tubacin only partially suppressed serum-starvation-induced LC3B-II deacetylation, suggesting that HDAC6 is not the only deacetylase acting on LC3B-II during serum-starvation-induced autophagy. Interestingly, tubacin-induced increase in LC3B-II acetylation was associated with p62/SQSTM1 accumulation upon serum starvation. HDAC6 knockdown did not influence autophagosome formation but resulted in impaired degradation of p62/SQSTM1 during serum starvation. Collectively, our data indicated that LC3B-II deacetylation, which was partly mediated by HDAC6, is involved in autophagic degradation during serum starvation.
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
Kun-Peng
KP
Liu
Dan
D
Zhou
Dong-Yun
DY
Ouyang
Li-Hui
LH
Xu
Yao
Y
Wang
Li-Xian
LX
Wang
Hao
H
Pan
Xian-Hui
XH
He
D000107:Acetylation; D000813:Anilides / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008247:Lysosomes / Q000502:physiology; D008561:Membrane Fusion; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D059748:Proteolysis
D000813:Anilides; D016895:Culture Media, Serum-Free; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C474316:tubacin; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
Autophagic degradation; Deacetylation; Histone deacetylase 6; Microtubule-associated protein 1 light chain 3