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线粒体自噬的机制:PINK1、帕金蛋白、USP30及其他相关蛋白

Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond.

作者信息

Bingol Baris, Sheng Morgan

机构信息

Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.

Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.

出版信息

Free Radic Biol Med. 2016 Nov;100:210-222. doi: 10.1016/j.freeradbiomed.2016.04.015. Epub 2016 Apr 16.


DOI:10.1016/j.freeradbiomed.2016.04.015
PMID:27094585
Abstract

Mitochondrial quality control is central for maintaining a healthy population of mitochondria. Two Parkinson's disease genes, mitochondrial kinase PINK1 and ubiquitin ligase Parkin, degrade damaged mitochondria though mitophagy. In this pathway, PINK1 senses mitochondrial damage and activates Parkin by phosphorylating Parkin and ubiquitin. Activated Parkin then builds ubiquitin chains on damaged mitochondria to tag them for degradation in lysosomes. USP30 deubiquitinase acts as a brake on mitophagy by opposing Parkin-mediated ubiquitination. Human genetic data point to a role for mitophagy defects in neurodegenerative diseases. This review highlights the molecular mechanisms of the mitophagy pathway and the recent advances in the understanding of mitophagy in vivo.

摘要

线粒体质量控制对于维持健康的线粒体群体至关重要。两个帕金森病相关基因,即线粒体激酶PINK1和泛素连接酶Parkin,通过线粒体自噬降解受损的线粒体。在这一途径中,PINK1感知线粒体损伤,并通过磷酸化Parkin和泛素来激活Parkin。激活后的Parkin随后在受损线粒体上构建泛素链,将其标记以便在溶酶体中降解。USP30去泛素酶通过对抗Parkin介导的泛素化作用,对线粒体自噬起到制动作用。人类遗传学数据表明线粒体自噬缺陷在神经退行性疾病中发挥作用。本综述重点介绍了线粒体自噬途径的分子机制以及体内线粒体自噬研究的最新进展。

相似文献

[1]
Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond.

Free Radic Biol Med. 2016-11

[2]
The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy.

Nature. 2014-6-4

[3]
Beyond Deubiquitylation: USP30-Mediated Regulation of Mitochondrial Homeostasis.

Adv Exp Med Biol. 2017

[4]
The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.

Genes Dev. 2015-5-15

[5]
Pharmacological inhibition of USP30 activates tissue-specific mitophagy.

Acta Physiol (Oxf). 2021-7

[6]
N-degron-mediated degradation and regulation of mitochondrial PINK1 kinase.

Curr Genet. 2020-8

[7]
Regulation by mitophagy.

Int J Biochem Cell Biol. 2014-8

[8]
PTEN-L is a novel protein phosphatase for ubiquitin dephosphorylation to inhibit PINK1-Parkin-mediated mitophagy.

Cell Res. 2018-6-22

[9]
Mechanism and regulation of the Lys6-selective deubiquitinase USP30.

Nat Struct Mol Biol. 2017-11

[10]
Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling.

Mol Cell. 2020-3-5

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[2]
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[3]
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Int J Mol Sci. 2025-7-25

[4]
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[5]
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[6]
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[7]
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[8]
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J Transl Med. 2025-5-23

[9]
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[10]
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