Acetylation of Hsc70 at K512 inhibits goat ovarian granulosa cell senescence by restoring chaperone-mediated autophagy.

Nonhistone acetylation plays a crucial role in key cellular processes associated with ageing, such as autophagy. Heat shock cognate protein 70 (Hsc70), a vital chaperone protein for chaperone-mediated autophagy (CMA), exerts a molecular chaperone function that is regulated by its acetylation status. However, the effects of this acetylation on CMA and granulosa cell senescence remain unclear. This study investigated the effects of Hsc70 acetylation on CMA activity and senescence in goat ovarian granulosa cells (GCs). Notably, Hsc70 acetylation was found to mitigate granulosa cell senescence and promote CMA activity. Mass spectrometry analysis identified Hsc70 K512 as the acetylation site, and Sirtuin 2 (Sirt2) was found to catalyze the deacetylation of this site. In addition, Hsc70 expression and CMA activity were significantly reduced in ageing ovaries and under oxidative stress conditions. Subsequent experiments revealed that deacetylated Hsc70 increased the early and late apoptotic rates of GCs and inhibited CMA activity. Functionally, acetylation of the Hsc70 K512 site alleviates the ageing of GCs. In conclusion, this study elucidates the molecular mechanism through which Hsc70 K512 acetylation alleviates cell senescence by enhancing CMA activity in goat ovarian GCs, providing novel insights and potential intervention targets for female mammalian reproduction.