Cardoso 2025 Biochim Biophys Acta Mol Basis Dis
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 |
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
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