RNA has a critical role in mitochondrial biology, mainly by mitochondrial DNA (mtDNA), which contains the genes for 13 oxidative phosphorylation essential proteins, 22 transfer RNAs (tRNAs), and 2 ribosomal RNAs (rRNAs) that are required for mitochondrial protein synthesis. These RNAs enable translation of mitochondrial-encoded proteins needed for ATP generation through the electron transport chain. Moreover, nuclear-encoded RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), control mitochondrial gene expression and function.
In addition, mitochondrial RNA processing and stability are essential for function, as abnormalities in RNA transcription, maturation, or degradation can cause mitochondrial disorders. Mutations in mtDNA targeting tRNAs or rRNAs tend to cause severe diseases such as mitochondrial encephalomyopathy or myoclonic epilepsy. Mitochondrial RNA also interacts with nuclear factors to regulate cellular energy demands and stress responses. In summary, mitochondrial RNA is essential for maintaining cellular energy metabolism, apoptosis regulation, and adaptation to metabolic stress.