pexophagy

Pexophagy is a selective form of autophagy in which peroxisomes are targeted for degradation in the lysosome or vacuole. It serves to regulate peroxisome number and quality, removing damaged or excess organelles as cells adapt to metabolic changes and environmental conditions.

In yeast, pexophagy can proceed through macropexophagy or micropexophagy. Macropexophagy packages whole peroxisomes into a double-membrane autophagosome, which then fuses with the vacuole for degradation; micropexophagy involves direct engulfment of peroxisomes by the vacuolar membrane. In both routes, selective recognition is mediated by peroxisome-specific receptors and adaptors that recruit core autophagy machinery. In yeast, receptors such as Atg30 or Atg36 facilitate this process by linking peroxisomes to Atg8/LC3 and other autophagy proteins. In mammalian cells, pexophagy is promoted by ubiquitination of peroxisomal proteins and adaptor receptors such as NBR1 and p62, which bind LC3 and connect ubiquitinated peroxisomes to the autophagy machinery.

Triggers for pexophagy include conditions that threaten peroxisome function or abundance, such as prolonged nutrient starvation, oxidative or metabolic stress, and defects in peroxisome biogenesis. Pexophagy works alongside peroxisome biogenesis to maintain organelle homeostasis, preventing accumulation of damaged peroxisomes and helping regulate lipid metabolism and reactive oxygen species handling.

Clinical and research relevance centers on the role of pexophagy in aging and disease. Dysregulation of pexophagy has been linked to various conditions, including neurodegenerative and metabolic disorders, highlighting its importance in cellular quality control and organelle turnover.