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首页> 外文期刊>Molecular cell >Bcl-2 family proteins participate in mitochondrial quality control by regulating parkin/PINK1-dependent mitophagy
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Bcl-2 family proteins participate in mitochondrial quality control by regulating parkin/PINK1-dependent mitophagy

机译：Bcl-2家族蛋白通过调节Parkin / PINK1依赖性线粒体参与线粒体质量控制

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摘要

Mitophagy facilitates the selective elimination of impaired or depolarized mitochondria through targeting the latter to autophagosomes. Parkin becomes localized to depolarized mitochondria in a PINK1-dependent manner and polyubiquitinates multiple mitochondrial outer membrane proteins. This permits ubiquitin-binding proteins (e.g., p62 and NBR1) to target impaired mitochondria to autophagosomes via Atg8/LC3II. Bcl-2 family proteins regulate mitochondrial outer membrane permeabilization during apoptosis and can also influence macroautophagy via interactions with Beclin-1. Here, we show that Parkin-dependent mitophagy is antagonized by prosurvival members of the Bcl-2 family (e.g., Bcl-xL and Mcl-1) in a Beclin-1-independent manner. Bcl-2 proteins suppressed mitophagy through inhibition of Parkin translocation to depolarized mitochondria. Consistent with this, Parkin translocation to mitochondria was enhanced by BH3-only proteins or a BH3-only mimetic. Taken together with their role as regulators of apoptosis-associated mitochondrial permeabilization, as well as mitochondrial fission/fusion dynamics, this suggests that Bcl-2 family proteins act as global regulators of mitochondrial homeostasis.
机译：线粒体通过将线粒体靶向自噬体，有助于选择性消除受损或去极化的线粒体。 Parkin以PINK1依赖的方式定位于去极化的线粒体，并且多泛素化多种线粒体外膜蛋白。这允许泛素结合蛋白（例如p62和NBR1）通过Atg8 / LC3II将受损的线粒体靶向自噬体。 Bcl-2家族蛋白调节细胞凋亡过程中的线粒体外膜通透性，并且还可以通过与Beclin-1相互作用来影响自噬。在这里，我们显示了以Beclin-1独立的方式被Bcl-2家族的生存成员（例如Bcl-xL和Mcl-1）拮抗的帕金依赖性线粒体。 Bcl-2蛋白通过抑制Parkin易位至去极化的线粒体来抑制线粒体。与此相一致，仅BH3蛋白或仅BH3模拟物增强了Parkin向线粒体的易位。连同其作为凋亡相关的线粒体通透性调节剂以及线粒体裂变/融合动力学的调节剂一起，这表明Bcl-2家族蛋白充当线粒体稳态的整体调节剂。

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