PTENα regulates mitophagy and maintains mitochondrial quality control

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 isoprenaline and ischemia-reperfusion. Mitochondrial clearance by mitophagy is also impaired in PTENα-deficient cardiomyocytes. In addition, we found PTENα physically interacts with the E3 ubiquitin ligase PRKN, which is an important mediator of mitophagy. PTENα 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 PTENα compromises mitochondrial translocation of PRKN and resultant mitophagy following mitochondrial depolarization. We propose that PTENα 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</p

Additional file 8 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S8. The sentences with PPIs and biological function information extracted from “BioCreAtIvE PPI” corpus by the PPIO-based method

Additional file 3 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S3.The sentences with protein-protein interactions in “BioCreAtIvE PPI” corpus

Additional file 13 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Supplementary Material and Methods

Additional file 4 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S4. The sentences with PPIs and PPI annotations mined manually from “BioCreAtIvE PPI” corpus

Additional file 5 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S5. Verbs and nouns used to construct Interaction Type sub-ontology

Additional file 11 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S11. The sentences with PPIs and detection method information extracted from “BioCreAtIvE PPI” corpus by the PPIO-based method

Additional file 2 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S2. Summary of PPI denoting words collected for PPI ontology construction

Additional file 7 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S7. The sentences with PPIs and subcellular location information extracted from “BioCreAtIvE PPI” corpus using the PPIO-based method

Additional file 9 of The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction

Table S9. The sentences with PPIs and interaction type information extracted from “BioCreAtIvE PPI” corpus by the PPIO-based method