| First Author | Cao Y | Year | 2019 |
| Journal | Nat Chem Biol | Volume | 15 |
| Issue | 12 | Pages | 1232-1240 |
| PubMed ID | 31740833 | Mgi Jnum | J:296117 |
| Mgi Id | MGI:6467702 | Doi | 10.1038/s41589-019-0399-y |
| Citation | Cao Y, et al. (2019) ABHD10 is an S-depalmitoylase affecting redox homeostasis through peroxiredoxin-5. Nat Chem Biol 15(12):1232-1240 |
| abstractText | S-Palmitoylation is a reversible lipid post-translational modification that has been observed on mitochondrial proteins, but both the regulation and functional consequences of mitochondrial S-palmitoylation are poorly understood. Here, we show that perturbing the 'erasers' of S-palmitoylation, acyl protein thioesterases (APTs), with either pan-active inhibitors or a mitochondrial-targeted APT inhibitor, diminishes the antioxidant buffering capacity of mitochondria. Surprisingly, this effect was not mediated by the only known mitochondrial APT, but rather by a resident mitochondrial protein with no known endogenous function, ABHD10. We show that ABHD10 is a member of the APT family of regulatory proteins and identify peroxiredoxin-5 (PRDX5), a key antioxidant protein, as a target of ABHD10 S-depalmitoylase activity. We then find that ABHD10 regulates the S-palmitoylation status of the nucleophilic active site residue of PRDX5, providing a direct mechanistic connection between ABHD10-mediated S-depalmitoylation of PRDX5 and its antioxidant capacity. |
