生物
粒体自噬
帕金
品脱1
线粒体
综合应力响应
细胞生物学
自噬
遗传学
基因
细胞凋亡
帕金森病
翻译(生物学)
疾病
病理
信使核糖核酸
医学
作者
Yogaditya Chakrabarty,Zheng Yang,Hsiuchen Chen,David C. Chan
出处
期刊:Molecular Cell
[Elsevier]
日期:2024-03-01
卷期号:84 (6): 1090-1100.e6
被引量:5
标识
DOI:10.1016/j.molcel.2024.01.016
摘要
Summary
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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