Non-coding RNAs: the dark side of nuclear-mitochondrial communication.

Mitochondria are critical hubs for the integration of several key metabolic processes implicated in cell growth and survival. They originated from bacterial ancestors through endosymbiosis, following the transfer of more than 90% of their endosymbiont genome to the host cell nucleus. Over time, a mutually beneficial symbiotic relationship has been established, which relies on continuous and elaborate signaling mechanisms between this life-essential organelle and its host. The ability of mitochondria to signal their functional state and trigger compensatory and adaptive cellular responses has long been recognized, but the underlying molecular mechanisms involved have remained poorly understood. Recent evidence indicates that non-coding RNAs (ncRNAs) may contribute to the synchronization of a series of essential cellular and mitochondrial biological processes, acting as "messengers" between the nucleus and the mitochondria. Here, we discuss the emerging putative roles of ncRNAs in various bidirectional signaling pathways established between the host cell and its mitochondria, and how the dysregulation of these pathways may lead to aging-related diseases, including cancer, and offer new promising therapeutic avenues.