Uppala 2017 Biochem Biophys Res Commun

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Uppala R, Dudiak B, Beck ME, Bharathi SS, Zhang Y, Stolz DB, Goetzman ES (2017) Aspirin increases mitochondrial fatty acid oxidation. Biochem Biophys Res Commun 482:346-51.

» PMID: 27856258

Uppala R, Dudiak B, Beck ME, Bharathi SS, Zhang Y, Stolz DB, Goetzman ES (2017) Biochem Biophys Res Commun

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.

Copyright © 2016 Elsevier Inc. All rights reserved.

Keywords: Aspirin, Fatty acid oxidation, Lysine acetylation, Mitochondria, Peroxisomes, SIRT3

O2k-Network Lab: CN Tianjin Zhang Y, US PA Pittsburgh Goetzman ES


Labels: MiParea: Respiration, Comparative MiP;environmental MiP, Pharmacology;toxicology  Pathology: Other 

Organism: Human, Mouse  Tissue;cell: HEK, Fibroblast  Preparation: Permeabilized cells 

Regulation: Fatty acid  Coupling state: LEAK, OXPHOS, ET  Pathway: N, NS  HRR: Oxygraph-2k