Cecatto 2023 BPS2023 San Diego

From Bioblast
Sabine Schmitt
Cecatto C, Schmitt Sabine, Cardoso L, Videja M, Dambrova M, Makrecka-Kuka M, Liepinsh E, Gnaiger E (2023) Contribution of fatty acid oxidation to respiratory control in brain mitochondria. 67th Annual Meeting of the Biophysical Society.

Link: Biophysical society annual meeting

Cecatto Cristiane, Schmitt Sabine, Cardoso Luiza, Videja Melita, Dambrova Maija, Makrecka-Kuka Marina, Liepinsh Edgars, Gnaiger Erich (2023)

Event: BPS2023 San Diego US

Glucose is the main energy source of the brain, yet recent studies demonstrate that fatty acid oxidation (FAO) in brain mitochondria supports oxidative phosphorylation (OXPHOS). Our study addressed the question how FAO in brain mitochondria (1) depends on the type and concentration of acylcarnitine, (2) influences carbohydrate-linked respiration, and (3) contributes to carbohydrate-linked OXPHOS capacity in comparison to respiratory control in kidney and cardiac mitochondria.

For evaluation of FAO capacity, we measured the increase of O2 flux (in the presence of ADP and 0.1 mM malate) induced by titration of acylcarnitines using the Oroboros O2k high-resolution respirometer. (1) In mouse brain homogenate, palmitoylcarnitine (PC) supported a higher FAO capacity compared to octanoylcarnitine (OC) but inhibited respiration at concentrations >10 Β΅M. (2) After titration of acylcarnitine or carrier, NADH-linked substrates (N: pyruvate, malate, glutamate), succinate (S), and glycerolphosphate (Gp) were titrated (NSGp-OXPHOS capacity). OC and PC neither stimulated nor inhibited NSGp-OXPHOS capacity. (3) Compared to brain homogenate, FAO capacity was higher in kidney homogenate and ― as expected ― much higher in permeabilized mouse cardiac fibers. Under these experimental conditions the ratio of FAO- to NS-OXPHOS capacity was 0.19 in heart, 0.08 in kidney, and only 0.012 in brain, suggesting a role for FAO in brain in terms of specific metabolic function but minor general bioenergetic relevance.

Our approach provides a toolkit for evaluation of optimal acylcarnitine concentrations to avoid inhibition and underestimation of FAO, and a baseline correction of respiration in the presence of low malate concentrations to avoid overestimation of FAO. These standard operating procedures are particularly important in brain mitochondria with FAO capacity as low as 1 % of carbohydrate-linked NS-OXPHOS capacity.


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


Affiliations and support

Cristiane Cecatto1, Sabine Schmitt1*, Luiza Cardoso1, Melita Videja2, Maija Dambrova2, Marina Makrecka-Kuka2, Edgars Liepinsh2, Erich Gnaiger1
  1. Oroboros Instruments, Innsbruck, Austria
  2. Latvian Institute of Organic Synthesis Laboratory of Pharmaceutical Pharmacology
* Presenting author
Supported by the European Union’s Horizon 2020 research and innovation program Grant 857394.


List of abbreviations, terms and definitions - MitoPedia

Β» MitoPedia: Terms and abbreviations


Labels: MiParea: Respiration 


Organism: Mouse  Tissue;cell: Heart, Nervous system, Kidney  Preparation: Permeabilized tissue, Homogenate 

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

FAT4BRAIN 

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