Expression of genes involved in mitochondrial protein import and mitochondrial stress response during ageing in the short-lived Nothobranchius furzeri

Ageing is associated with several defects at the molecular and cellular level and can accumulate to produce age-related pathophysiologies. Often underlying these pathophysiologies are deficits in mitochondrial function which decline during ageing due to increased oxidative stress and mutations in mitochondrial DNA, mitochondrial proteins and membranes. Fortunately, cells and specifically mitochondria, have developed several protective responses to mitigate stress and its deleterious effects. One of these responses is the mitochondrial unfolded protein response (UPRmt), which is activated under different conditions which can include when mitochondrial protein import is impaired. UPRmt helps maintain mitochondrial proteostasis during stress by promoting transcription of genes encoding mitochondrial chaperones (mtHsp60, mtHsp70, Hspe1) and proteases (Lonp1). These chaperones are known to fold unfolded or misfolded proteins, while the proteases degrade aggregated proteins in the mitochondrial matrix. However, little is still known about the evolution of UPRmt during ageing. For this reason, our aim is to determine whether gene expression and protein levels of these components involved in both mitochondrial import and UPRmt is affected by brain ageing in Nothobranchius furzeri. We found that HSP60, HSP70 and LONP1 expression decreased after 6 weeks of age. In contrast, the gene expression of HSPE1 remained unchanged within the ageing brain. Further, when we measured Hsp60 protein levels, we also observed that protein level was not impacted by brain ageing. As a way forward, it would be interesting to conduct studies that confirm whether or not mitochondrial import is altered with age. This could be done by measuring the matrix levels of certain proteins across age. Similarly, conducting studies on proteins that are exclusively expressed when UPRmt is activated could provide information on whether the levels of these specific proteins change with age.