First Author | Sirey TM | Year | 2019 |
Journal | Elife | Volume | 8 |
PubMed ID | 31045494 | Mgi Jnum | J:288665 |
Mgi Id | MGI:6359617 | Doi | 10.7554/eLife.45051 |
Citation | Sirey TM, et al. (2019) The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity. Elife 8:e45051 |
abstractText | To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation and, with miR-488-3p, represent novel targets for the modulation of complex I activity. |