The mitochondrial‐derived lncRNA MDL1 mediates a mitochondria‐to‐nucleus retrograde regulation by inhibiting the nuclear translocation of p53

It has been clear that mitochondria are not just nucleus‐relying entities; instead, they also modulate nuclear events reversely. Long noncoding RNAs (lncRNAs) are classified into nuclear‐encoded and mitochondrial‐derived lncRNAs (nulncRNAs and mtlncRNAs, respectively). Relative to nulncRNAs, the mtlncRNAs are far from being well characterized. Here we report a mtlncRNA, MDL1, that interacts with both p53 and Tid1 proteins and acts as retrograde signaling. MDL1 can regulate a network of nuclear genes, including p53 targets, and functions in cells in a p53‐dependent manner. Mechanistically, MDL1 is necessary for maintenance of the reciprocal interaction between p53 and Tid1, thereby facilitating formation of a ternary MDL1/p53/Tid1 complex that inhibits the nuclear translocation of p53. Since p53 is a canonical transcription factor, the observed inhibition of p53 nuclear translocation would contribute to the MDL1‐mediated mitochondrial retrograde regulation on nuclear genes expression. This study advances our understanding of lncRNA biology, and also sheds new light on the role of mtlncRNAs in mitochondrial‐nuclear functional network and in diverse biological processes.