Author Correction: PTEN-L is a novel protein phosphatase for ubiquitin dephosphorylation to inhibit PINK1-Parkin-mediated mitophagy
Autor: | Yih-Cherng Liou, Yin Shi, Hanry Yu, Jianbin Zhang, Han-Ming Shen, Shuo Deng, Liming Wang, Yik-Lam Cho, Guang Lu, Pornteera Pawijit, Boon-Huat Bay, Kah-Leong Lim, Hayden Weng-Siong Tan, Jingzi Zhang, Yajun Wu, Yihua Wu, Jigang Wang, Yancheng Tang, Celestial T. Yap, Yan Tong, Lei Fang, Hui-Ying Chan, Grace Gui-Yin Lim, Mallilankaraman Karthik, Jung Eun Park, Ritu Chawla, Siu Kwan Sze, Chunxin Wang |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
biology Novel protein Phosphatase Correction PINK1 Cell Biology Parkin Article Cell biology Dephosphorylation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Ubiquitin Mitophagy biology.protein PTEN Molecular Biology 030217 neurology & neurosurgery |
Zdroj: | Cell Research |
ISSN: | 1748-7838 |
Popis: | Mitophagy is an important type of selective autophagy for specific elimination of damaged mitochondria. PTEN-induced putative kinase protein 1 (PINK1)-catalyzed phosphorylation of ubiquitin (Ub) plays a critical role in the onset of PINK1–Parkin-mediated mitophagy. Phosphatase and tensin homolog (PTEN)-long (PTEN-L) is a newly identified isoform of PTEN, with addition of 173 amino acids to its N-terminus. Here we report that PTEN-L is a novel negative regulator of mitophagy via its protein phosphatase activity against phosphorylated ubiquitin. We found that PTEN-L localizes at the outer mitochondrial membrane (OMM) and overexpression of PTEN-L inhibits, whereas deletion of PTEN-L promotes, mitophagy induced by various mitochondria-damaging agents. Mechanistically, PTEN-L is capable of effectively preventing Parkin mitochondrial translocation, reducing Parkin phosphorylation, maintaining its closed inactive conformation, and inhibiting its E3 ligase activity. More importantly, PTEN-L reduces the level of phosphorylated ubiquitin (pSer65-Ub) in vivo, and in vitro phosphatase assay confirms that PTEN-L dephosphorylates pSer65-Ub via its protein phosphatase activity, independently of its lipid phosphatase function. Taken together, our findings demonstrate a novel function of PTEN-L as a protein phosphatase for ubiquitin, which counteracts PINK1-mediated ubiquitin phosphorylation leading to blockage of the feedforward mechanisms in mitophagy induction and eventual suppression of mitophagy. Thus, understanding this novel function of PTEN-L provides a key missing piece in the molecular puzzle controlling mitophagy, a critical process in many important human diseases including neurodegenerative disorders such as Parkinson’s disease. |
Databáze: | OpenAIRE |
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