Histone deacetylase 10 knockout activates chaperone-mediated autophagy and accelerates the decomposition of its substrate.

Histone deacetylase (HDAC) 10 is a member of class IIb HDACs, but its deacetylation targets and functions are poorly characterized. Recent investigation has proposed that HDAC10 deacetylates heat shock cognate protein 70 kDa (HSC70) after interaction. HSC70 plays an important role in chaperone-mediated autophagy (CMA), binding CMA substrates and transporting them to lysosomes. However, it has not been clarified whether HDAC10 is involved in CMA. In this study, we established the HDAC10 knockout HeLa cell line and evaluated its CMA activity to determine whether HDAC10 participates in regulating CMA. In HDAC10 knockout cells, lysosome-associated protein type 2A (LAMP2A) protein level increased and LAMP2A-positive lysosomes accumulated around the nucleus. Moreover, GAPDH, which is a well-known CMA substrate, was delivered to LAMP2A-positive lysosomes and degraded in HDAC10 knockout cells more efficiently than in wild type HeLa cells. These results suggest that CMA is activated in HDAC10 knockout cells. Meanwhile, turnover assay using LC3 and p62, which are macroautophagy markers, indicated that autophagic flux was fully functioning in HDAC10 knockout cells as well as in wild type HeLa cells. In conclusion, HDAC10 participated in regulating CMA, and HDAC10 knockout activated CMA and accelerated degradation of a CMA substrate.