| Title | Identification of an autoinhibitory, mitophagy-inducing peptide derived from the transmembrane domain of USP30 |
| Authors | Qin, Xuan Wang, Rui Xu, Hongkun Tu, Licheng Chen, Hailing Li, Heng Liu, Na Wang, Jinpeng Li, Shuiming Yin, Feng Xu, Naihan Li, Zigang |
| Affiliation | Peking Univ, Sch Chem Biol & Biotechnol, State Key Lab Chem Oncogen, Shenzhen Grad Sch, Shenzhen, Peoples R China Pingshan Translat Med Ctr, Shenzhen Bay Lab, Shenzhen, Peoples R China Tsinghua Univ, Tsinghua Shenzhen Int Grad Sch, Inst Biopharmaceut & Hlth Engn, Shenzhen, Peoples R China Shenzhen Univ, Coll Life Sci & Oceanog, Shenzhen, Peoples R China |
| Keywords | DEUBIQUITINATING ENZYME MITOCHONDRIAL MORPHOLOGY ENDOPLASMIC-RETICULUM MASS-SPECTROMETRY UBIQUITIN CHAINS FISSION FUSION PROTEIN PARKIN MECHANISM |
| Issue Date | Jan-2022 |
| Publisher | AUTOPHAGY |
| Abstract | The mitochondrial-anchored deubiquitinating enzyme USP30 (ubiquitin specific peptidase 30) antagonizes PRKN/parkin-mediated mitophagy, making it a potential target for treating Parkinson disease. However, few inhibitors targeting USP30 have been reported. Here, we report a novel peptide (Q14) derived from the transmembrane (TM) domain of USP30 that can target mitochondrial-anchored USP30 directly and increase mitophagy through two intriguing and distinct mechanisms: a novel autoinhibition mechanism in USP30 and accelerated autophagosome formation via the LC3-interacting region (LIR) of the Q14 peptide. We identified the potential binding sites between the Q14 peptide and USP30 and postulated that an allosteric autoinhibition mechanism regulates USP30 activity. Furthermore, the LIR motif in the Q14 peptide offers additional binding with LC3 and accelerated autophagosome formation. The two mechanisms synergistically enhance mitophagy. Our work provides novel insight and direction to the design of inhibitors for USP30 or other deubiquitinating enzymes (DUBs). |
| URI | http://hdl.handle.net/20.500.11897/634636 |
| ISSN | 1554-8627 |
| DOI | 10.1080/15548627.2021.2022360 |
| Indexed | SCI(E) |
| Appears in Collections: | 化学生物学与生物技术学院 å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
