Paradoxical Mitophagy Regulation by PINK1 and TUFm

Lin, Jingjing; Cui, Kai; Chen, Wenfeng; Yao, Yizhou; Ni, Shiwei; Ye, Meina; Zhuang, Gui-Feng; Hu, Minhuang; Gao, Jun; Gao, Caixi; Liu, Yan; Yang, Mingjuan; Zhang, Zhenkun; Zhang, Xiaohui; Huang, Jiexiang; Chen, Fei; Zhang, Xi; Yu, Shasha; Chen, Yuling; Jiang, Yating; Wang, Shujuan; Yang, Xiaozhen; Liu, Ke; Zhou, Hai‐Meng; Ji, Zhiliang; Deng, Haiteng; Haque, M. Emdadul; Li, Junxiang; Mi, Li-Zhi; Li, Yuexi; Yang, Yufeng

doi:10.1016/j.molcel.2020.10.007

Cited by 46 publications

(34 citation statements)

References 58 publications

(65 reference statements)

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“…Upon mitophagy initiation, however, stabilized PINK1 phosphorylates mitochondrial TUFm at serine 222 resulting in its cytosolic relocalization where it interferes with ATG5-ATG12 conjugation and thus suppresses mitophagy. The proposed mechanism suggests that PINK1 can buffer its activity resulting in suppression of excessive mitophagy [265]. Furthermore, [266,267].…”

Section: Pink1/parkin-mediated Mitophagymentioning

confidence: 99%

Sensing, signaling and surviving mitochondrial stress

Eckl

Krumwiede

Fessler

et al. 2021

Cell. Mol. Life Sci.

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Mitochondrial fidelity is a key determinant of longevity and was found to be perturbed in a multitude of disease contexts ranging from neurodegeneration to heart failure. Tight homeostatic control of the mitochondrial proteome is a crucial aspect of mitochondrial function, which is severely complicated by the evolutionary origin and resulting peculiarities of the organelle. This is, on one hand, reflected by a range of basal quality control factors such as mitochondria-resident chaperones and proteases, that assist in import and folding of precursors as well as removal of aggregated proteins. On the other hand, stress causes the activation of several additional mechanisms that counteract any damage that may threaten mitochondrial function. Countermeasures depend on the location and intensity of the stress and on a range of factors that are equipped to sense and signal the nature of the encountered perturbation. Defective mitochondrial import activates mechanisms that combat the accumulation of precursors in the cytosol and the import pore. To resolve proteotoxic stress in the organelle interior, mitochondria depend on nuclear transcriptional programs, such as the mitochondrial unfolded protein response and the integrated stress response. If organelle damage is too severe, mitochondria signal for their own destruction in a process termed mitophagy, thereby preventing further harm to the mitochondrial network and allowing the cell to salvage their biological building blocks. Here, we provide an overview of how different types and intensities of stress activate distinct pathways aimed at preserving mitochondrial fidelity.

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Section: Pink1/parkin-mediated Mitophagymentioning

confidence: 99%

Sensing, signaling and surviving mitochondrial stress

Eckl

Krumwiede

Fessler

et al. 2021

Cell. Mol. Life Sci.

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“…EFTU has mitochondrial-cytosolic dual localization. Ser222 of EFTU is phosphorylated by PINK1, which localizes it mainly in the cytosol and plays a role in inhibiting mitophagy ( Lin et al, 2020 ).…”

Section: Mitochondrial Translation Elongation and Diseasementioning

confidence: 99%

Mitochondrial Protein Translation: Emerging Roles and Clinical Significance in Disease

Wang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Mitochondria are one of the most important organelles in cells. Mitochondria are semi-autonomous organelles with their own genetic system, and can independently replicate, transcribe, and translate mitochondrial DNA. Translation initiation, elongation, termination, and recycling of the ribosome are four stages in the process of mitochondrial protein translation. In this process, mitochondrial protein translation factors and translation activators, mitochondrial RNA, and other regulatory factors regulate mitochondrial protein translation. Mitochondrial protein translation abnormalities are associated with a variety of diseases, including cancer, cardiovascular diseases, and nervous system diseases. Mutation or deletion of various mitochondrial protein translation factors and translation activators leads to abnormal mitochondrial protein translation. Mitochondrial tRNAs and mitochondrial ribosomal proteins are essential players during translation and mutations in genes encoding them represent a large fraction of mitochondrial diseases. Moreover, there is crosstalk between mitochondrial protein translation and cytoplasmic translation, and the imbalance between mitochondrial protein translation and cytoplasmic translation can affect some physiological and pathological processes. This review summarizes the regulation of mitochondrial protein translation factors, mitochondrial ribosomal proteins, mitochondrial tRNAs, and mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in the mitochondrial protein translation process and its relationship with diseases. The regulation of mitochondrial protein translation and cytoplasmic translation in multiple diseases is also summarized.

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“…Ubiquitylation of mitochondrial proteins by Parkin is finally decoded by the autophagy machinery that captures the damaged organelles, by assembling an autophagosomal membrane around ubiquitinated mitochondria, and drives their degradation via lysosomal fusion. Remarkably, PINK1 recruits also autophagy receptors optineurin (OPTN) and nuclear dot protein 52 kDa (NDP52) in a Parkin-independent way [60,61], and it is able to negatively regulate mitophagy via TUFm [62]. Although the PINK1/TUFm role may appear quite contradictory, their antagonizing activity may represent a safeguard mechanism to tightly regulate homeostasis, preventing excessive mitophagy or counteracting false positive activation of mitochondrial degradation.…”

Section: Parkinson's Disease and Mitochondria: A Tight Bond Underlying Pathogenic Mechanismmentioning

confidence: 99%

PGC-1s in the Spotlight with Parkinson’s Disease

Piccinin

Sardanelli

Seibel

et al. 2021

IJMS

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Parkinson’s disease is one of the most common neurodegenerative disorders worldwide, characterized by a progressive loss of dopaminergic neurons mainly localized in the substantia nigra pars compacta. In recent years, the detailed analyses of both genetic and idiopathic forms of the disease have led to a better understanding of the molecular and cellular pathways involved in PD, pointing to the centrality of mitochondrial dysfunctions in the pathogenic process. Failure of mitochondrial quality control is now considered a hallmark of the disease. The peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) family acts as a master regulator of mitochondrial biogenesis. Therefore, keeping PGC-1 level in a proper range is fundamental to guarantee functional neurons. Here we review the major findings that tightly bond PD and PGC-1s, raising important points that might lead to future investigations.

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Paradoxical Mitophagy Regulation by PINK1 and TUFm

Cited by 46 publications

References 58 publications

Sensing, signaling and surviving mitochondrial stress

Sensing, signaling and surviving mitochondrial stress

Mitochondrial Protein Translation: Emerging Roles and Clinical Significance in Disease

PGC-1s in the Spotlight with Parkinson’s Disease

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