Bcl-xL inhibits PINK1/Parkin-dependent mitophagy by preventing mitochondrial Parkin accumulation

Yu, Shaohua; Du, Mingde; Yin, Ao; Mai, Zihao; Wang, Yong; Zhao, Mengxin; Wang, Xiaoping; Chen, Tongsheng

doi:10.1016/j.biocel.2020.105720

Cited by 23 publications

(16 citation statements)

References 64 publications

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“…Overexpression of pro-survival BCL-2 family proteins, and specifically BCL-x L , in cultured cell lines has been shown to inhibit Parkin translocation to the OMM (Hollville et al 2014;Yu et al 2020;Zhang et al 2020). This seems contradictory to the pro-survival role of BCL-x L , as this would decrease the amount of mitophagy, thereby increasing the risk of dysfunctional mitochondria generating ROS.…”

Section: Influence Of Bcl-2 Family Proteins On Parkin Translocationmentioning

confidence: 99%

Kill one or kill the many: interplay between mitophagy and apoptosis

Wanderoy

Hees

Klesse

et al. 2020

Biological Chemistry

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Mitochondria are key players of cellular metabolism, Ca2+ homeostasis, and apoptosis. The functionality of mitochondria is tightly regulated, and dysfunctional mitochondria are removed via mitophagy, a specialized form of autophagy that is compromised in hereditary forms of Parkinson’s disease. Through mitophagy, cells are able to cope with mitochondrial stress until the damage becomes too great, which leads to the activation of pro-apoptotic BCL-2 family proteins located on the outer mitochondrial membrane. Active pro-apoptotic BCL-2 proteins facilitate the release of cytochrome c from the mitochondrial intermembrane space (IMS) into the cytosol, committing the cell to apoptosis by activating a cascade of cysteinyl-aspartate specific proteases (caspases). We are only beginning to understand how the choice between mitophagy and the activation of caspases is determined on the mitochondrial surface. Intriguingly in neurons, caspase activation also plays a non-apoptotic role in synaptic plasticity. Here we review the current knowledge on the interplay between mitophagy and caspase activation with a special focus on the central nervous system.

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Section: Influence Of Bcl-2 Family Proteins On Parkin Translocationmentioning

confidence: 99%

Kill one or kill the many: interplay between mitophagy and apoptosis

Wanderoy

Hees

Klesse

et al. 2020

Biological Chemistry

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“…The relationship between mitophagy and apoptosis is supported by evidence of physical interactions between several players of each process. First, the anti-apoptotic BCL-2 proteins Bcl-xL and MCL1 were shown to prevent mitophagy by physically interacting with Parkin, preventing its stable recruitment to mitochondria (Hollville et al, 2014;Yu et al, 2020). Second, the Bcl-2 pro-apoptotic family member BNIP3 is also a mitophagy receptor that physically interacts with LC3, via its LIR domain, promoting mitophagy.…”

Section: Interaction Between Mitophagic and Apoptotic Componentsmentioning

confidence: 99%

Role of Mitofusins and Mitophagy in Life or Death Decisions

Joaquim

Escobar-Henriques

2020

Front. Cell Dev. Biol.

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Mitochondria entail an incredible dynamism in their morphology, impacting death signaling and selective elimination of the damaged organelles. In turn, by recycling the superfluous or malfunctioning mitochondria, mostly prevalent during aging, mitophagy contributes to maintain a healthy mitochondrial network. Mitofusins locate at the outer mitochondrial membrane and control the plastic behavior of mitochondria, by mediating fusion events. Besides deciding on mitochondrial interconnectivity, mitofusin 2 regulates physical contacts between mitochondria and the endoplasmic reticulum, but also serves as a decisive docking platform for mitophagy and apoptosis effectors. Thus, mitofusins integrate multiple bidirectional inputs from and into mitochondria and ensure proper energetic and metabolic cellular performance. Here, we review the role of mitofusins and mitophagy at the crossroad between life and apoptotic death decisions. Furthermore, we highlight the impact of this interplay on disease, focusing on how mitofusin 2 and mitophagy affect non-alcoholic fatty liver disease.

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“…5 C ). Moreover, the prosurvival protein Bcl-X L actually represses mitophagy by direct binding to parkin and hindering its translocation to mitochondria in various stressed cells ( 179 , 180 , 181 ). In addition, PINK1 can phosphorylate Bcl-X L on the MOM of CCCP-treated SH-SY5Y cells, not regulating mitophagy but rather suppressing apoptosis by preventing the proapoptotic cleavage of Bcl-X L ( 182 ).…”

Section: Roles Of Accessory Factorsmentioning

confidence: 99%

Regulation of mitochondrial cargo-selective autophagy by posttranslational modifications

Terradas

Zittlau

Maček

et al. 2021

Journal of Biological Chemistry

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show abstract

Bcl-xL inhibits PINK1/Parkin-dependent mitophagy by preventing mitochondrial Parkin accumulation

Cited by 23 publications

References 64 publications

Kill one or kill the many: interplay between mitophagy and apoptosis

Kill one or kill the many: interplay between mitophagy and apoptosis

Role of Mitofusins and Mitophagy in Life or Death Decisions

Regulation of mitochondrial cargo-selective autophagy by posttranslational modifications

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