ATM functions at the peroxisome to induce pexophagy in response to ROS Academic Article uri icon

Overview

MeSH Major

  • Ataxia Telangiectasia Mutated Proteins
  • Autophagy
  • Peroxisomes
  • Reactive Oxygen Species
  • Receptors, Cytoplasmic and Nuclear

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.

publication date

  • October 3, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4589490

Digital Object Identifier (DOI)

  • 10.1038/ncb3230

PubMed ID

  • 26344566

Additional Document Info

start page

  • 1259

end page

  • 69

volume

  • 17

number

  • 10