Journal: Military Medical Research
Article Title: USP18 exacerbates myocardial I/R injury by inhibiting Parkin mitophagy through the deubiquitinase PTEN-L
doi: 10.1016/j.mmr.2026.100004
Figure Lengend Snippet: USP18 aggravates cardiac I/R injury through regulation of mitochondria and inhibition of mitophagy. a Electron microscopy image showing mitophagy in USP18-cKO mouse hearts ( n= 5). Scale bar=3 μm. White arrowheads indicate sites of mitophagy. b Protein levels of PINK1, Parkin, ubiquitinated proteins (Ub), P62, and LC3II in mitochondria from heart tissue in USP18-cKO and WT mice 24 h after I/R injury ( n =4). c Electron microscopy image showing mitophagy in USP18-overexpres (OV) mouse hearts ( n =5). Scale bar=3 μm. White arrowheads indicate sites of mitophagy. d Protein levels of PINK1, Parkin, Ub, P62, and LC3II proteins in mitochondria from the heart tissue of USP18-OV mice 24 h after I/R injury ( n =4). Color shift in mitophagy dye (red) and lysosomal dye (green) in NRVMs showing mitophagy in NRVMs with USP18 siRNA transfection ( e ) or Ad-USP18 infection ( f ) and the quantitative mitophagy index in each group ( n= 5). Scale bar=9 μm. Protein levels of PINK1, Parkin, Ub, P62, and LC3II in mitochondria from NRVMs transfected with USP18 siRNA ( g ) or infected with Ad-USP18 ( h ). ⁎⁎ P <0.01, ⁎⁎⁎ P <0.001 ⁎⁎⁎⁎ P <0.0001. USP18. Ubiquitin-specific protease 18; I/R. Ischemia/reperfusion; WT. Wild-type; KO. Knockout; P62. Sequestosome 1; LC3. Microtubule-associated protein 1 light chain 3; VDAC. Voltage-dependent anion channel.
Article Snippet: To block mitophagy, the selective dynamin-related protein 1 (Drp1) inhibitor Mdivi-1 was used (50 μmol/L, MedChemExpress, USA).
Techniques: Inhibition, Electron Microscopy, Transfection, Infection, Ubiquitin Proteomics, Knock-Out
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