Journal
NATURE CHEMICAL BIOLOGY
Volume 15, Issue 12, Pages 1232-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41589-019-0399-y
Keywords
-
Categories
Funding
- University of Chicago
- National Institute of General Medical Sciences of the National Institutes of Health [R35 GM119840]
- 'Catalyst Award' from Chicago Biomedical Consortium
- Searle Funds at The Chicago Community Trust
- National Institute of General Medical Sciences from the National Institutes of Health [P41 GM103403]
- DOE Office of Science [DE-AC02-06CH11357]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available