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Arias-Reyes 2023 MitoFit

From Bioblast
Publications in the MiPMap
Arias-Reyes C, Aliaga-Raduán F, Pinto-Aparicio R, Joseph V, Soliz J (2023) Mitochondrial plasticity in the retrosplenial cortex enhances ATP synthesis during acclimatization to hypoxia in mice but not in rats. MitoFit Preprints 2023.6.

» MitoFit Preprints 2023.6.

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Mitochondrial plasticity in the retrosplenial cortex enhances ATP synthesis during acclimatization to hypoxia in mice but not in rats.

Arias-Reyes Christian, Aliaga-Raduan Fernanda, Pinto-Aparicio Renata, Joseph Vincent, Soliz Jorge (2023) MitoFit Prep

Abstract: Acclimatization to high altitude relies on adjustments of cellular metabolism that optimize oxygen use and energy production. In tissues with high energy demand and almost exclusive reliance on aerobic metabolism such as the brain, hypoxia is a particularly strong stressor, however, strategies to adjust metabolic pathways for successful high-altitude acclimatization remain poorly understood. Compared to SD rats, FVB mice show successful acclimatization to high altitude, we, therefore, used this model to investigate metabolic adjustments in the retrosplenial cortex (a key area of the brain involved in spatial learning and navigation) in normoxia and during acclimatization to hypoxia (12 % O2 – 1, 7, and 21 days). We measured in simultaneous the rates of ATP synthesis and O2 consumption in fresh permeabilized brain samples by coupled high-resolution respirometry and fluorometry. We quantified the citrate synthase (CS) activity as an index of mitochondrial content, the transcriptional regulation of genes involved in mitochondrial dynamics; and the activity of enzymes representative of the glycolytic, aerobic, and anaerobic metabolism. Our findings show that acclimatization to hypoxia significantly increases ATP synthesis in mice and to a lower extent in rats. In mice, this occurs in parallel with a reduction of O2 consumption, and a three-fold increase in the P»/O ratio. In rats, a six-fold increase in CS activity and altered mitochondrial dynamics gene expression are evident. Finally, activities of glycolytic, aerobic, or anaerobic enzymes remain overall unchanged in both species except for a transient glycolytic and anaerobic peak at day 7 in mice. Altogether, our results show that chronic hypoxia optimizes the efficiency of mitochondrial ATP synthesis in the retrosplenial cortex of mice. Contrastingly, rats sustain the production of ATP only by increasing mitochondrial content and altering mitochondrial dynamics, suggesting drastic mitochondrial malfunctions.
Keywords: Acclimatization to hypoxia; high altitude; mitochondria; brain; metabolism Bioblast editor: Tindle-Solomon L O2k-Network Lab: CA Quebec Soliz J

Labels: MiParea: Respiration 

Stress:Hypoxia  Organism: Mouse, Rat  Tissue;cell: Nervous system  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k