SQSTM1 facilitates oocyte maturation through inducing ACLY degradation mediated by selective autophagy

Abstract

ABSTRACT Selective autophagy specifically eliminates certain intracellular substrates through the autophagy pathway. Organelles and aggregation-prone proteins can be degraded through the autophagy receptor protein SQSTM1/p62, which renders them a promising therapeutic approach against infertility. He et al. demonstrate that blocking of autophagy in cumulus granulosa cells can directly attenuate citrate levels and in turn affect oocyte maturation quality. Further findings show that SQSTM1 connects K63-polyubiquitinated ACLY (ATP citrate lyase) during the process of selective autophagic degradation, which further compromises the homeostasis of citrate. Therefore, the quality of oocyte meiotic maturation can be evaluated by the levels of selective autophagy in cumulus granulosa cells.