Cardoso 2024 MitoFit FAO

Cardoso LHD, Cecatto C, Ozola M, Korzh S, Zvejniece L, Gukalova B, Doerrier C, Dambrova M, Makrecka-Kuka M, Gnaiger E, Liepinsh E (2024) Fatty acid β-oxidation in brain mitochondria: Insights from high-resolution respirometry in mouse, rat and Drosophila brain, ischemia and aging models. MitoFit Preprints 2023.10. https://doi.org/10.26124/mitofit:2023-0010.v2

» MitoFit Preprints 2023.10.v2.

Fatty acid β-oxidation in brain mitochondria: Insights from high-resolution respirometry in mouse, rat and Drosophila brain, ischemia and aging models

Cardoso Luiza HD, Cecatto Cristiane, Ozola Melita, Korzh Stanislava, Zvejniece Liga, Gukalova Baiba, Doerrier Carolina, Dambrova Maija, Makrecka-Kuka Marina, Gnaiger Erich, Liepinsh Edgars (2024) MitoFit Prep

Abstract:

Version 2 (v2) 2024-07-30

Version 1 (v1) 2023-11-22 - »Link to all versions«

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 β-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 10 µM which corresponds to the total concentration of LC acylcarnitines in the brain. Maximal respiration with octanoylcarnitine was reached at 20 µM, 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.

• Keywords: brain; nervous system; mitochondrial function; fatty acid oxidation; beta-oxidation; acylcarnitines; respirometry. • Bioblast editor: Cardoso LHD • O2k-Network Lab: AT Innsbruck Oroboros, LV Riga Liepins E

ORCID: Luiza H. D. Cardoso, Cristiane Cecatto, Melita Ozola, Stanislava Korzh, Liga Zvejniece, Baiba Gukalova, Carolina Doerrier, Maija Dambrova, Marina Makrecka-Kuka, Erich Gnaiger, Edgars Liepinsh

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: OXPHOS, ET  Pathway: F, N, S, Gp 

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