MicroRNA miR-122 is Important in Improved Mitochondrial Function Resulting from Calorie Restriction

Calorie restriction improves near all measures of metabolic health, mitochondrial function included. Mitochondria are the power plants of the cell, and they accumulate damage and dysfunction with age, in part because the processes of quality control intended to remove worn and broken mitochondria falter. Calorie restriction improves the situation, but, characteristically, does so in a very broad way that makes it challenging to pick out the important mechanisms from the many other sweeping changes in cellular activity. Researchers here suggest that upregulation of miR-122 is noteworthy, but it is just one of many changes noted in the paper.

Both caloric restriction (CR) and mitochondrial proteostasis are linked to longevity, but how CR maintains mitochondrial proteostasis in mammals remains elusive. MicroRNAs (miRNAs) are well known for gene silencing in cytoplasm and have recently been identified in mitochondria, but knowledge regarding their influence on mitochondrial function is limited.

Here, we report that CR increases miRNAs, which are required for the CR-induced activation of mitochondrial translation, in mouse liver. The ablation of miR-122, the most abundant miRNA induced by CR, or the retardation of miRNA biogenesis via Drosha knockdown significantly reduces the CR-induced activation of mitochondrial translation. Importantly, CR-induced miRNAs cause the overproduction of mitochondrial DNA encoded proteins, which induces the mitochondrial unfolded protein response (UPRmt), and consequently improves mitochondrial proteostasis and function.

These findings establish a physiological role of miRNA-enhanced mitochondrial function during CR and reveal miRNAs as critical mediators of CR in inducing UPRmt to improve mitochondrial proteostasis.

Link: https://doi.org/10.1016/j.isci.2019.06.028

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