PTEN-L puts a brake on mitophagy

Liming Wang, Jigang Wang, Yancheng Tang, Han Ming Shen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

12 Citations (Scopus)


Mitophagy is a main type of selective autophagy, via which damaged mitochondria are selectively degraded via the autophagic pathway. The protein kinase PINK1 and E3 ubiquitin ligase PRKN are the most well studied regulators of mitophagy, via a feedforward mechanism involving ubiquitin phosphorylation (p-Ser65-Ub) and accumulation at the damaged mitochondria. However, it is unknown whether there is a protein phosphatase against PINK1-mediated phosphorylation of ubiquitin. We recently reported that PTEN-L, a newly identified PTEN isoform, is a novel negative regulator of mitophagy through dephosphorylation of p-Ser65-Ub. Our data demonstrate that a significant portion of PTEN-L localizes at the outer mitochondrial membrane and is able to prevent PRKN’s mitochondrial translocation, reduce the phosphorylation of PRKN, impair its E3 ligase activity as well as maintain PRKN in a closed/inactive status. Moreover, we found that PTEN-L dephosphorylates p-Ser65-Ub to disrupt the feedforward mechanism of mitophagy. Our findings suggest that PTEN-L acts as a brake in the regulation of mitophagy. Abbreviations: ATR: alternatively translated region; CCCP: carbonylcyanide 3-chlorophenylhydrazone; DUBs: deubiquitinating enzymes; MFN2: mitofusion2; MS/MS: tandem mass spectrometry; mtDNA: mitochondrial DNA; MTS: mitochondrial targeting sequences; O/A: oligomycin and antimycin A; PINK1: PTEN induced putative kinase 1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PTEN: phosphatase and tensin homolog; PTEN-L: phosphatase and tensin homolog-long; Ub: ubiquitin; USP: ubiquitin-specific proteases; YFP: yellow fluorescence protein.

Original languageEnglish
Pages (from-to)2023-2025
Number of pages3
Issue number11
Early online date2 Sept 2018
Publication statusPublished - 2 Nov 2018

Scopus Subject Areas

  • Molecular Biology
  • Cell Biology

User-Defined Keywords

  • Mitophagy
  • phosphatase
  • PRKN
  • PTEN-L
  • ubiquitin


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