Cardoso 2025 Biochim Biophys Acta Mol Basis Dis

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Cardoso LHD, Cecatto C, Ozola M, Korzh S, Zvejniece L, Gukalova B, Doerrier C, Dambrova M, Makrecka-Kuka M, Gnaiger E, Liepinsh E (2025) Fatty acid Ξ²-oxidation in brain mitochondria: Insights from high-resolution respirometry in mouse, rat and Drosophila brain, ischemia and aging models. Biochim Biophys Acta Mol Basis Dis 1871:167544. https://doi.org/10.1016/j.bbadis.2024.167544

Β» PMID: 39424161 Open Access

Cardoso Luiza HD, Cecatto Cristiane, Ozola Melita, Korzh Stanislava, Zvejniece Liga, Gukalova Baiba, Doerrier Carolina, Dambrova Maija, Makrecka-Kuka Marina, Gnaiger Erich, Liepinsh Edgars (2025) Biochim Biophys Acta Mol Basis Dis

Abstract: Glucose is the main energy source of the brain, yet recent studies demonstrate that fatty acid oxidation (FAO) plays a relevant role in the pathogenesis of central nervous system disorders. We evaluated FAO in brain mitochondria under physiological conditions, in the aging brain, and after stroke. Using high-resolution respirometry we compared medium-chain (MC, octanoylcarnitine) and long-chain (LC, palmitoylcarnitine) acylcarnitines as substrates of Ξ²-oxidation in the brain. The protocols developed avoid FAO overestimation by malate-linked anaplerotic activity in brain mitochondria. The capacity of FA oxidative phosphorylation (F-OXPHOS) with palmitoylcarnitine was up to 4 times higher than respiration with octanoylcarnitine. The optimal concentration of palmitoylcarnitine was 10β€―ΞΌM which corresponds to the total concentration of LC acylcarnitines in the brain. Maximal respiration with octanoylcarnitine was reached at 20β€―ΞΌM, however, this concentration exceeds MC acylcarnitine concentrations in the brain 15 times. F-OXPHOS capacity was highest in mouse cerebellum, intermediate in cortex, prefrontal cortex, and hypothalamus, and hardly detectable in hippocampus. F-OXPHOS capacity was 2-fold lower and concentrations of LC acylcarnitines were 2-fold higher in brain of aged rats. A similar trend was observed in the rat model of endothelin-1-induced stroke, but reduction of OXPHOS capacity was not limited to FAO. In conclusion, although FAO is not a dominant pathway in brain bioenergetics, it deserves specific attention in studies of brain metabolism.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: AT Innsbruck Oroboros, LV Riga Liepins E

MitoFit Preprint

Β» Cardoso 2024 MitoFit FAO


Labels: MiParea: Respiration  Pathology: Aging;senescence  Stress:Ischemia-reperfusion  Organism: Mouse, Rat, Drosophila  Tissue;cell: Heart, Nervous system, Kidney  Preparation: Homogenate 

Regulation: Substrate, Fatty acid  Coupling state: ET, OXPHOS  Pathway: F, N, S, Gp  HRR: Oxygraph-2k 

2024-10 

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