Expression of genes involved in the mitochondrial unfolded protein response during brain aging in Nothobranchius furzeri

Various changes associated with brain aging in mitochondrial function and dynamics contribute to a decline in the organelle function. Among them, the alteration of mitochondrial proteostasis leads to an accumulation of unfolded proteins that can cause deleterious effects on mitochondria. Due to the essential roles performed by mitochondria, maintaining their integrity is crucial to ensure cell and organism viability and preserve cellular function. To counteract stressful conditions within the mitochondria, the organelle deploy a defensive mechanism called the mitochondrial unfolded protein response (UPRmt). This signal transduction pathway between mitochondria and nuclei allows the induction of genes involved in stabilizing mitochondrial function, including genes encoding mitochondrial chaperones and proteases, to upregulate protein quality control and restore mitochondrial homeostasis. So far, UPRmt has never been studied in the aging brain. Yet, this energy-intensive organ is particularly prone to develop mitochondrial dysfunctions. Therefore, the objective of this thesis was to identify whether aging causes sufficient mitochondrial stress to trigger UPRmt in the brain. To address this objective, expression of key UPRmt genes was determined in N. furzeri brain samples of different ages. The abundance of the main UPRmt regulatory transcription factor was also measured across brain aging. Overall, the data suggest that aging is not a sufficient stress to trigger UPRmt. Nevertheless, other avenues need to be explored to better understand the activation of the response in the aging brain of N. furzeri and its impact on life expectancy and fish development.