Peroxisomal protein PEX13 functions in selective autophagy

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Peroxisome biogenesis disorders (PBDs), such as Zellweger syndrome spectrum (ZSS) disorders, are linked to mutations in peroxin (PEX) genes.
• ZSS disorders cause severe neurological, hepatic, and renal abnormalities, often leading to neonatal death, with impaired peroxisome function considered the primary cause.
• The precise mechanisms underlying ZSS pathogenesis remain incompletely understood.

Purpose of the Study:

• To investigate the role of PEX13 beyond peroxisome import.
• To determine if PEX13 is involved in selective autophagy pathways.
• To assess the impact of disease-associated PEX13 mutations on its cellular functions.

Main Methods:

• Utilized cell-based assays to examine the function of PEX13 in selective autophagy.
• Investigated the role of PEX13 in virophagy (viral clearance) and mitophagy (damaged mitochondria removal).
• Analyzed specific PEX13 mutants (I326T and W313G) for defects in mitophagy.

Main Results:

• Demonstrated that PEX13 is essential for selective autophagy, specifically for virophagy and mitophagy.
• Identified that disease-associated PEX13 mutants I326T and W313G exhibit impaired mitophagy.
• Showed that PEX13's mitophagy function is shared with PEX3 but distinct from PEX14 and PEX19, which are involved in general autophagy.

Conclusions:

• PEX13 plays a critical role in selective autophagy processes.
• Dysfunctional PEX13-mediated mitophagy may be a contributing factor to the pathogenesis of Zellweger spectrum disorders.
• This study expands the known functions of PEX13 and offers new insights into PBDs.