Decoding mitochondrial–nuclear (epi)genome interactions: the emerging role of ncRNAs

Bidirectional communication between the mitochondria and the nucleus is required for several physiological processes, and the nuclear epigenome is a key mediator of this relationship. ncRNAs are an emerging area of discussion for their roles in cellular function and regulation. In this review, we highlight the role of mitochondrial-encoded ncRNAs as mediators of communication between the mitochondria and the nuclear genome. We focus primarily on retrograde signaling, a process in which the mitochondrion relays ncRNAs to translate environmental stress signals to changes in nuclear gene expression, with implications on stress responses that may include disease(s). Other biological roles of mitochondrial-encoded ncRNAs, such as mitochondrial import of proteins and regulation of cell signaling, will also be discussed. Communication between the nucleus (the cell control center) and the mitochondria (the energy-producing factories of the cell) is important for keeping cells working properly. Though communication goes both ways, signals sent from the mitochondria to the nucleus have become a big topic of discussion because they have been found to affect disease. ncRNAs are another topic that has been gaining traction. These are RNA transcripts that, instead of coding for proteins, have other roles in controlling our cells. Here we discuss ncRNAs that come from the mitochondria, called mt-ncRNAs. By sending mt-ncRNAs to the nucleus, mitochondria can send messages to the nucleus to help cells adapt to stress or changes in the environment. These mt-ncRNAs demonstrate the importance of mitochondria in controlling our cells. By studying this process, we gain information that helps in treating diseases. The emerging role of mitochondrial-encoded ncRNAs as mediators of the mitochondrial–nuclear signaling pathway, eliciting adaptive nuclear gene expression changes in response to environmental stress.