Dataset Information

PTEN? regulates mitophagy and maintains mitochondrial quality control.

ABSTRACT: PTEN plays an important role in tumor suppression, and PTEN family members are involved in multiple biological processes in various subcellular locations. Here we report that PTEN?, the first identified PTEN isoform, regulates mitophagy through promotion of PARK2 recruitment to damaged mitochondria. We show that PTEN?-deficient mice exhibit accumulation of cardiac mitochondria with structural and functional abnormalities, and PTEN?-deficient mouse hearts are more susceptible to injury induced by isoprenaline and ischemia-reperfusion. Mitochondrial clearance by mitophagy is also impaired in PTEN?-deficient cardiomyocytes. In addition, we found PTEN? physically interacts with the E3 ubiquitin ligase PRKN, which is an important mediator of mitophagy. PTEN? binds PRKN through the membrane binding helix in its N-terminus, and promotes PRKN mitochondrial translocation through enhancing PRKN self-association in a phosphatase-independent manner. Loss of PTEN? compromises mitochondrial translocation of PRKN and resultant mitophagy following mitochondrial depolarization. We propose that PTEN? functions as a mitochondrial quality controller that maintains mitochondrial function and cardiac homeostasis.

Abbreviations

BECN1 beclin 1; CCCP carbonyl cyanide m-chlorophenylhydrazone; FBXO7 F-box protein 7; FS fraction shortening; HSPA1L heat shock protein family A (Hsp70) member 1 like; HW: BW heart weight:body weight ratio; I-R ischemia-reperfusion; ISO isoprenaline; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; MBH membrane binding helix; MFN1 mitofusin 1; MFN2 mitofusin 2; Nam nicotinamide; TMRM tetramethylrhodamine ethyl ester; WGA wheat germ agglutinin.

SUBMITTER: Li G

PROVIDER: S-EPMC6135630 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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PTENα regulates mitophagy and maintains mitochondrial quality control.

Li Guoliang G Yang Jingyi J Yang Chunyuan C Zhu Minglu M Jin Yan Y McNutt Michael A MA Yin Yuxin Y

Autophagy 20180801 10

PTEN plays an important role in tumor suppression, and PTEN family members are involved in multiple biological processes in various subcellular locations. Here we report that PTENα, the first identified PTEN isoform, regulates mitophagy through promotion of PARK2 recruitment to damaged mitochondria. We show that PTENα-deficient mice exhibit accumulation of cardiac mitochondria with structural and functional abnormalities, and PTENα-deficient mouse hearts are more susceptible to injury induced by ...[more]

PMID: 29969932

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