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

Area of Science:

• Cell Biology
• Reproductive Biology
• Molecular Mechanisms

Background:

• Selective autophagy degrades specific intracellular components via the autophagy pathway.
• The autophagy receptor protein SQSTM1/p62 mediates the degradation of organelles and protein aggregates.
• Dysregulation of cellular processes in granulosa cells can impact oocyte quality and fertility.

Purpose of the Study:

• To investigate the role of selective autophagy in cumulus granulosa cells during oocyte maturation.
• To determine the impact of autophagy inhibition on citrate levels and oocyte quality.
• To elucidate the molecular connection between SQSTM1/p62, ATP citrate lyase (ACLY), and citrate homeostasis.

Main Methods:

• Inhibition of autophagy in cumulus granulosa cells.
• Measurement of intracellular citrate levels.
• Assessment of oocyte meiotic maturation quality.
• Analysis of SQSTM1/p62 and K63-polyubiquitinated ACLY interactions.

Main Results:

• Blocking autophagy in cumulus granulosa cells directly reduced citrate levels.
• Impaired autophagy led to compromised oocyte maturation quality.
• SQSTM1/p62 was found to link K63-polyubiquitinated ACLY during selective autophagic degradation.
• This process further disrupted citrate homeostasis.

Conclusions:

• Selective autophagy in cumulus granulosa cells is essential for maintaining citrate homeostasis and ensuring oocyte meiotic maturation quality.
• The SQSTM1/p62-ACLY axis is a key component of selective autophagy involved in regulating citrate levels.
• Oocyte maturation quality can potentially be assessed by evaluating selective autophagy levels in cumulus granulosa cells.