Mitochondrial ncRNAs beyond the mitochondrion: coordinators of organelle crosstalk

The mitochondrion contains its own genome that encodes subunits of respiratory complexes, components of the translation machinery, and numerous non-coding RNAs (ncRNAs). Some of these ncRNAs are antisense transcripts of their respective genes, regulating their maturation within mitochondria. Others facilitate mitochondria-to-nucleus communication, conveying mitochondrial status to the nucleus and coordinating synergy between the genomes. The first known mito-ncRNAs that exit mitochondria were those generated from the control regions of the mitochondrial genome. Recent evidence suggests this phenomenon is broader, encompassing multiple mitochondrial sense and antisense transcripts and mito-tRNAs. mito-ncRNAs are regulated by the proliferative state of the cell, physiological stresses, and viral infections. Both within and outside the organelle, mito-ncRNAs serve as scaffolds for protein complex assembly, as modulators of promoter occupancy, heterochromatin states, nucleolar functions, and spliceosome selectivity, and as precursors and regulators of miRNA networks. Here, we summarize and discuss current knowledge regarding mito-ncRNA-mediated signaling pathways.