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Biochem Biophys Res Commun. 2017 Jan 8;482(2):346-351. doi: 10.1016/j.bbrc.2016.11.066. Epub 2016 Nov 14.

Aspirin increases mitochondrial fatty acid oxidation.

Author information

1
Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States.
2
Center for Biologic Imaging, Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15260, United States.
3
Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States. Electronic address: Eric.goetzman@chp.edu.

Abstract

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders.

KEYWORDS:

Aspirin; Fatty acid oxidation; Lysine acetylation; Mitochondria; Peroxisomes; SIRT3

PMID:
27856258
PMCID:
PMC5195905
DOI:
10.1016/j.bbrc.2016.11.066
[Indexed for MEDLINE]
Free PMC Article

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