| First Author | Li G | Year | 2018 |
| Journal | Autophagy | Volume | 14 |
| Issue | 10 | Pages | 1742-1760 |
| PubMed ID | 29969932 | Mgi Jnum | J:308567 |
| Mgi Id | MGI:6717807 | Doi | 10.1080/15548627.2018.1489477 |
| Citation | Li G, et al. (2018) PTENalpha regulates mitophagy and maintains mitochondrial quality control. Autophagy 14(10):1742-1760 |
| abstractText | 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 PTENalpha, the first identified PTEN isoform, regulates mitophagy through promotion of PARK2 recruitment to damaged mitochondria. We show that PTENalpha-deficient mice exhibit accumulation of cardiac mitochondria with structural and functional abnormalities, and PTENalpha-deficient mouse hearts are more susceptible to injury induced by isoprenaline and ischemia-reperfusion. Mitochondrial clearance by mitophagy is also impaired in PTENalpha-deficient cardiomyocytes. In addition, we found PTENalpha physically interacts with the E3 ubiquitin ligase PRKN, which is an important mediator of mitophagy. PTENalpha 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 PTENalpha compromises mitochondrial translocation of PRKN and resultant mitophagy following mitochondrial depolarization. We propose that PTENalpha 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. |
