Unravelling a small non-coding RNA interface between the mitochondrial and nuclear genomes
Cell Biology
Final Report Abstract
Mitochondria are crucial for cell function and can respond to stress, such as that caused by mitochondrial DNA (mtDNA) damage, through various stress response pathways. For example, stressed, dysfunctional mitochondria can signal to the nucleus via the mitochondrial unfolded protein response (UPRMT), or be cleared from the cell altogether by mitophagy. However, how different mitochondrial stress response pathways are regulated is not clear. Here, we show that upregulation of one miRNA (referred to as protective miRNA, miR-p) partially restores cell function in a Caenorhabditis elegans model of chronic mtDNA damage, by suppressing the translation of the UPRMT transcription factor DVE-1 and the mitophagy factor LGG-2. Expression of miR-p is collaboratively induced by master regulators of the UPRMT (ATFS-1), the insulin signalling pathway (DAF-16) and the hypoxia stress response (HIF-1a). Our findings suggest that regulating the UPRMT and mitophagy can be beneficial and demonstrate a role for miR-p in decelerating these responses and protecting cells under mitochondrial stress.
