How long noncoding RNAs enforce their will on mitochondrial activity: regulation of mitochondrial respiration, reactive oxygen species production, apoptosis, and metabolic reprogramming in cancer.

The cellular transcriptome contains a wide diversity of untranslated RNAs, of which the class of regulatory long noncoding RNAs (lncRNAs) has only recently been recognized. Evidence swiftly accumulates of lncRNAs influencing mitochondrial activities of eukaryotic cells, and perturbed expression is conspicuously associated with human diseases. In this review, we describe the multifaceted effects of lncRNAs on mitochondrial function, more particularly on the balance between oxidative phosphorylation and glycolysis, on the production of reactive oxygen species, and on apoptosis in human cells. Emphasis is placed on the involvement of lncRNAs in cancer metabolism, as tumor cells rely heavily on modifications of mitochondrial functioning as an essential component for sustained tumorigenesis and cancer progression. From the nonexhaustive list of lncRNAS described in this review, ANRIL, AScmtRNA, H19, HOTAIR, LincRNA-p21, MALAT1, RMRP, SAMMSON, and VL30 have emerged as potent regulators of mitochondrial metabolism. Due to their key role in cancer progression, they represent potential targets of innovative lncRNA-based treatment strategies.