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Fig. 7 | Molecular Cancer

Fig. 7

From: Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives

Fig. 7

Overview of the major proteins of Pexophagy. Under normal circumstances, the mTORC1-mediated proteasome pathway can maintain low PEX2 expression levels. Under starvation conditions, an increase in PEX2 causes PEX5 and PMP70 to get ubiquitinated, which ultimately triggers Pexophagy in an NBR1-dependent way. USP30 offsets PEX2 by deubiquitinating its substrate to prevent Pexophagy. The initial response mechanism of peroxisome ROS is ATM serine/threonine kinase. TSC2 is induced by activated ATM kinase, and mTORC1 is inhibited by activated TSC2. Additionally, ATM phosphorylates PEX5 at Ser141, which causes PEX5 to be ubiquitinated at Lys209. After that, ubiquitinated PEX5 attaches itself to p62/NBR1 to trigger reactive oxygen species autophagy. The proteophage target of ubiquitin-dependent peroxisome is monobititinated PEX5 on Cys11. PEX1 and PEX6, which are affixed to the peroxisome by PEX26, will ubiquitinate PEX5 and remove it from the membrane after transit. Thus far, ACBD5 is the sole protein that is specific to phagocytic cells. Recruitment of Pexophagy-specific receptors or adapters may be facilitated by ACBD5

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