Reference - Detail
| RRC ID | 88149 |
|---|---|
| Author | Kirmes I, Hung GCC, Hahn A, Dai CY, Campbell D, Ahier A, Lee RSY, Palmer A, Zuryn S. |
| Title | The microRNA miR-71 suppresses maladaptive UPRmt signaling through both cell-autonomous and cell-non-autonomous mechanisms. |
| Journal | Nat Commun |
| Abstract |
Mitochondria play a central role in metabolism and biosynthesis, but function also as platforms that perceive and communicate environmental and physiological stressors to the nucleus and distal tissues. Systemic mitochondrial signaling is thought to synchronize and amplify stress responses throughout the whole body, but during severe or chronic damage, overactivation of mitochondrial stress pathways may be maladaptive and exacerbate aging and metabolic disorders. Here we uncover a protective micro(mi)RNA response to mtDNA damage in Caenorhabditis elegans that prolongs tissue health and function by interfering with mitochondrial stress signaling. Acting within muscle cells, we show that the miRNA miR-71 is induced during severe mitochondrial damage by the combined activities of DAF-16, HIF-1, and ATFS-1, where it restores sarcomere structure and animal locomotion by directly suppressing the inordinate activation of DVE-1, a key regulator of the mitochondrial unfolded protein response (UPRmt). Indirectly, miR-71 also reduces the levels of multiple neuro- and insulin-like peptides and their secretion machinery, resulting in decreased cell-non-autonomous signaling of mitochondrial stress from muscle to glia cells. miR-71 therefore beneficially coordinates the suppression of both local and systemic mitochondrial stress pathways during severe organelle dysfunction. These findings open the possibility that metabolic disorders could be ameliorated by limiting the overactivation of mitochondrial stress responses through targeted small RNAs. |
| Volume | 17(1) |
| Pages | 510 |
| Published | 2025-12-14 |
| DOI | 10.1038/s41467-025-67198-2 |
| PII | 10.1038/s41467-025-67198-2 |
| PMID | 41392100 |
| PMC | PMC12804905 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism DNA, Mitochondrial / genetics DNA, Mitochondrial / metabolism Forkhead Transcription Factors MicroRNAs* / genetics MicroRNAs* / metabolism Mitochondria* / genetics Mitochondria* / metabolism Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism Unfolded Protein Response* / genetics |
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| The most frequently cited source | News |
| Total number of mentions | 15 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm4525 tm12973 tm4803 |