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线粒体内膜的暴露引发凋亡性线粒体自噬。

Exposure of the inner mitochondrial membrane triggers apoptotic mitophagy.

机构信息

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.

Ubiquitin Signalling Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.

出版信息

Cell Death Differ. 2024 Mar;31(3):335-347. doi: 10.1038/s41418-024-01260-2. Epub 2024 Feb 23.


DOI:10.1038/s41418-024-01260-2
PMID:38396150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10923902/
Abstract

During apoptosis mediated by the intrinsic pathway, BAX/BAK triggers mitochondrial permeabilization and the release of cytochrome-c, followed by a dramatic remodelling of the mitochondrial network that results in mitochondrial herniation and the subsequent release of pro-inflammatory mitochondrial components. Here, we show that mitochondrial herniation and subsequent exposure of the inner mitochondrial membrane (IMM) to the cytoplasm, initiates a unique form of mitophagy to deliver these damaged organelles to lysosomes. IMM-induced mitophagy occurs independently of canonical PINK1/Parkin signalling and is driven by ubiquitination of the IMM. Our data suggest IMM-induced mitophagy is an additional safety mechanism that cells can deploy to contain damaged mitochondria. It may have particular relevance in situations where caspase activation is incomplete or inhibited, and in contexts where PINK1/Parkin-mitophagy is impaired or overwhelmed.

摘要

在内在途径介导的细胞凋亡过程中,BAX/BAK 触发线粒体通透性的增加和细胞色素 c 的释放,随后线粒体网络发生剧烈重塑,导致线粒体突起和随后释放促炎的线粒体成分。在这里,我们表明线粒体突起和随后的内线粒体膜(IMM)暴露到细胞质中,启动了一种独特的形式的线粒体自噬,将这些受损的细胞器递送到溶酶体中。IMM 诱导的线粒体自噬独立于经典的 PINK1/Parkin 信号通路发生,并且由 IMM 的泛素化驱动。我们的数据表明,IMM 诱导的线粒体自噬是细胞可以用来包含受损线粒体的另一种安全机制。它在半胱天冬酶激活不完全或受到抑制的情况下,以及在 PINK1/Parkin 介导的线粒体自噬受损或被压倒的情况下,可能具有特殊的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/603fc9279989/41418_2024_1260_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/3ee922157cfa/41418_2024_1260_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/66669ab679ff/41418_2024_1260_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/162edc976f71/41418_2024_1260_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/af1689a63130/41418_2024_1260_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/f97b09ed0647/41418_2024_1260_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/603fc9279989/41418_2024_1260_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/3ee922157cfa/41418_2024_1260_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/66669ab679ff/41418_2024_1260_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/162edc976f71/41418_2024_1260_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/af1689a63130/41418_2024_1260_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/f97b09ed0647/41418_2024_1260_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/10923902/603fc9279989/41418_2024_1260_Fig6_HTML.jpg

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本文引用的文献

[1]
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[2]
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