ATM Functions at the Peroxisome to Induce Pexophagy in Response to ROS

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2015 Sep 8

PMID 26344566

Citations 223

Authors

Jiangwei Zhang

Durga Nand Tripathi

Ji Jing

Angela Alexander

Jinhee Kim

Reid T Powell

Ruhee Dere

Jacqueline Tait-Mulder

Ji-Hoon Lee

Tanya T Paull

Raj K Pandita

Vijaya K Charaka

Tej K Pandita

Michael B Kastan

Cheryl Lyn Walker

Affiliations

Soon will be listed here.

Abstract

Peroxisomes are highly metabolic, autonomously replicating organelles that generate reactive oxygen species (ROS) as a by-product of fatty acid β-oxidation. Consequently, cells must maintain peroxisome homeostasis, or risk pathologies associated with too few peroxisomes, such as peroxisome biogenesis disorders, or too many peroxisomes, inducing oxidative damage and promoting diseases such as cancer. We report that the PEX5 peroxisome import receptor binds ataxia-telangiectasia mutated (ATM) and localizes this kinase to the peroxisome. In response to ROS, ATM signalling activates ULK1 and inhibits mTORC1 to induce autophagy. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. These data reveal an important new role for ATM in metabolism as a sensor of ROS that regulates pexophagy.

Citing Articles

Pexophagy and Oxidative Stress: Focus on Peroxisomal Proteins and Reactive Oxygen Species (ROS) Signaling Pathways.

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PMID: 40002313 PMC: 11851658. DOI: 10.3390/antiox14020126.

Peroxisome and pexophagy in neurological diseases.

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A Novel Peroxisome-Related Gene Signature Predicts Breast Cancer Prognosis and Correlates with T Cell Suppression.

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