Peroxisomes are dynamic organelles that metabolize fatty acids and reactive oxygen species. When peroxisomes become damaged, superfluous, or metabolically obsolete, cells remove them through pexophagy, a form of selective autophagy that preserves cellular homeostasis and prevents oxidative stress. Work by Suresh Subramani at University of California San Diego and reviews by Daniel J. Klionsky at University of Michigan explain the core idea that selective recognition, tagging, and delivery to the autophagy machinery drive pexophagy.
Recognition and ubiquitination
The first step in selective degradation is molecular tagging. Peroxisomal membrane proteins, especially the import receptor PEX5, can be modified by ubiquitination. Ubiquitin conjugation is carried out by peroxisomal E3 ligase complexes and serves as a signal for selective autophagy. Subramani at University of California San Diego emphasizes that the pattern of ubiquitination distinguishes normal recycling from pexophagy targeting. Monoubiquitination tends to mark proteins for recycling while polyubiquitination marks them for removal.
Receptors and autophagosome recruitment
Once tagged, peroxisomes are recognized by autophagy receptors that bridge ubiquitin on the organelle to the autophagosomal membrane through interactions with ATG8 family proteins such as LC3. In mammalian cells, receptors including NBR1 and p62 bind ubiquitin-decorated peroxisomes and recruit the isolation membrane. Daniel J. Klionsky at University of Michigan has reviewed how these selective receptors couple cargo to core autophagy machinery, while Yoshinori Ohsumi at Tokyo Institute of Technology provided foundational insights into autophagosome formation that underpin these interactions.
Failure of efficient pexophagy has physiological and pathological consequences. Rudolf J. Wanders at Radboud University Medical Center documents that impaired peroxisome turnover contributes to metabolic dysfunction and can exacerbate disorders characterized by defective peroxisomal biogenesis. In tissues with high peroxisomal activity such as liver and kidney, defective clearance increases oxidative burden and can influence systemic metabolism. Cultural and environmental contexts matter because exposure to certain pollutants or dietary lipids alters peroxisomal workload and may change reliance on pexophagy for cellular resilience.
Overall, selective degradation of peroxisomal proteins in pexophagy relies on specific tagging by ubiquitin, recognition by adaptor receptors, and envelopment by autophagosomes. Contemporary reviews and experimental studies by Subramani at University of California San Diego, Klionsky at University of Michigan, Ohsumi at Tokyo Institute of Technology, and Wanders at Radboud University Medical Center collectively support this mechanistic framework and its relevance to human health.