@article{a9eeb8507c6b45d6b1e70b1aff61eb9b,
title = "ATM functions at the peroxisome to induce pexophagy in response to ROS",
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.",
author = "Jiangwei Zhang and Tripathi, {Durga Nand} and Ji Jing and Angela Alexander and Jinhee Kim and Powell, {Reid T.} and Ruhee Dere and Jacqueline Tait-Mulder and Lee, {Ji Hoon} and Paull, {Tanya T.} and Pandita, {Raj K.} and Charaka, {Vijaya K.} and Pandita, {Tej K.} and Kastan, {Michael B.} and Walker, {Cheryl Lyn}",
note = "Funding Information: We thank S. Subramani (University of California, San Diego, California) for critical advice and providing the mRFP–EGFP–SKL plasmids, and M. Mancini (Baylor College of Medicine, Houston, Texas for providing the DsRed–SKL plasmid. We are also grateful for the assistance of K. Dunner (U.T.M.D. Cancer Center, Houston, Texas) and D. Townley (Baylor College of Medicine, Houston, Texas) in electron microscopy image acquisition. This work was supported by National Institutes of Health (NIH) Grant R01 CA143811 to C.L.W., a Robert A. Welch Endowed Chair in Chemistry (BE-0023) to C.L.W., and NIH grants CA129537, CA154320 and GM109768 to T.K.P. J.J. was a recipient of the China Scholarship Council (CSC). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = oct,
day = "3",
doi = "10.1038/ncb3230",
language = "English (US)",
volume = "17",
pages = "1259--1269",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Research",
number = "10",
}