Q14 is a peptide derived from the transmembrane domain of the mitochondrial anchored deubiquitinating enzyme USP30 (ubiquitin specific peptidase 30). Q14 can easily cross the cell membrane, bind to mitochondrial anchored USP30 directly, degrade outer mitochondrial membrane (OMM) proteins, promote mitochondrial fission, and trigger mitophagy. Q14 increases mitophagy through two distinct mechanisms, autoinhibition of USP30, and accelerated autophagosome formation through the LC3-interacting region (LIR) of Q14, synergistically enhancing mitophagy. USP30 antagonises PRKN/parkin-mediated mitophagy, making it a potential target for treating Parkinsons disease.
