PRKN-IMMT/MIC60 axis promotes myocardial ischemia-reperfusion injury via lysosomal degradation of GPX4

: ATG5, autophagy related 5; ATP, adenosine triphosphate; CCCP, carbonyl cyanide m-chlorophenylhydrazone; CHX, cycloheximide; cKO, cardiomyocyte-specific knockout; CQ, chloroquine; CRISPR, clustered regularly interspaced short palindromic repeats; EF, ejection fraction; Fer-1, ferrostatin-1; FS, fractional shortening; GO, Gene Ontology; GPX4, glutathione peroxidase 4; GST, glutathione S-transferase; gRNA, guide RNA; hiPSC-CMs, human induced pluripotent stem cell-derived cardiomyocytes; H/R, hypoxia-reoxygenation; IF, immunofluorescence; IHC, immunohistochemistry; IMMT/MIC60, inner membrane mitochondrial protein; IP, immunoprecipitation; LoxP, locus of X-overP1; KO, knockout; KR, lysine residues mutated to arginine; MDA, malondialdehyde; MFN2, mitofusin 2; MIR, myocardial ischemia reperfusion; MMP, mitochondrial membrane potential; mPTP, mitochondrial permeability transition pore; mtROS, mitochondrial reactive oxygen species; NAC, N-acetylcysteine; OMM, outer mitochondrial membrane; PRKN, parkin RBR E3 ubiquitin protein ligase; RAB7, RAB7, member RAS oncogene family; RNA-seq, RNA sequencing; UB, ubiquitin; WB, western blot; WT, wild-type.