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The HRI branch of the integrated stress response selectively triggers mitophagy.
Chakrabarty, Yogaditya; Yang, Zheng; Chen, Hsiuchen; Chan, David C.
Afiliação
  • Chakrabarty Y; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Yang Z; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Chen H; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Chan DC; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: dchan@caltech.edu.
Mol Cell ; 84(6): 1090-1100.e6, 2024 Mar 21.
Article em En | MEDLINE | ID: mdl-38340717
ABSTRACT
To maintain mitochondrial homeostasis, damaged or excessive mitochondria are culled in coordination with the physiological state of the cell. The integrated stress response (ISR) is a signaling network that recognizes diverse cellular stresses, including mitochondrial dysfunction. Because the four ISR branches converge to common outputs, it is unclear whether mitochondrial stress detected by this network can regulate mitophagy, the autophagic degradation of mitochondria. Using a whole-genome screen, we show that the heme-regulated inhibitor (HRI) branch of the ISR selectively induces mitophagy. Activation of the HRI branch results in mitochondrial localization of phosphorylated eukaryotic initiation factor 2, which we show is sufficient to induce mitophagy. The HRI mitophagy pathway operates in parallel with the mitophagy pathway controlled by the Parkinson's disease related genes PINK1 and PARKIN and is mechanistically distinct. Therefore, HRI repurposes machinery that is normally used for translational initiation to trigger mitophagy in response to mitochondrial damage.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Mitofagia Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Mitofagia Idioma: En Ano de publicação: 2024 Tipo de documento: Article