Open AccessABHD10 is an S-depalmitoylase affecting redox homeostasis through peroxiredoxin-5
Author(s) -
Yang Cao,
Tian Qiu,
Rahul S. Kathayat,
Saara-Anne Azizi,
Anneke K. Thorne,
Daniel Ahn,
Yuko Fukata,
Masaki Fukata,
Phoebe A. Rice,
Bryan C. Dickinson
Publication year - 2019
Publication title -
nature chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.412
H-Index - 216
eISSN - 1552-4469
pISSN - 1552-4450
DOI - 10.1038/s41589-019-0399-y
Subject(s) - palmitoylation , peroxiredoxin , mitochondrion , microbiology and biotechnology , biology , biochemistry , oxidative phosphorylation , chemistry , cysteine , enzyme , peroxidase
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.