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. 2020 Jan 16;21(2):578. doi: 10.3390/ijms21020578

Figure 4.

Figure 4

Regulation of mammalian pexophagy. Schematic of ubiquitin-independent and ubiquitin-dependent pexophagy resulting from intracellular and extracellular cues. Amino acid starvation relieves mTORC1 inhibition of the peroxisomal E3 ubiquitin ligase PEX2, allowing PEX2 to ubiquitinate peroxisomal proteins PMP70 and PEX5 and facilitating NBR1 and p62-mediated pexophagy. LC3-II-PEX14 interactions promote pexophagy in an amino acid starvation-dependent mechanism. Increased reactive oxygen species (ROS) levels result in ATM–PEX5 interactions at the peroxisome that promote PEX5 phosphorylation by ATM and ubiquitination by PEX2, to facilitate p62-mediated pexophagy. Hypoxia relieves VHL-mediated inhibition of HIF-2a, resulting in PEX5 ubiquitination by an unknown E3 ubiquitin ligase and NBR1-mediated pexophagy. The peroxisomal AAA-type ATPase complex PEX1-PEX6-PEX26 opposes PEX5-ubiquitination and pexophagy.