Expanding the Coding Potential of the Mitochondrial Genome with MitoRiboSeq

The mitochondrial genome encodes 13 well-characterized mRNAs but, similar to the nuclear genome, it has the potential to encode many additional proteins through previously unannotated open reading frames. Using MitoRiboSeq, we detected dozens of new mitochondrial-derived microproteins in both cell lines and liver tissues. We demonstrate that MOTS-c, a previously described microprotein, shows a significant decrease during senescence induction, and its supplementation is sufficient to prevent key cellular dysfunctions associated with this process. This work significantly deepens our understanding of the mitochondrial genome and underscores its relevance for functional and therapeutic discoveries. Overall design: Expression profiling by high throughput sequencing