| RRC ID |
88149
|
| 著者 |
Kirmes I, Hung GCC, Hahn A, Dai CY, Campbell D, Ahier A, Lee RSY, Palmer A, Zuryn S.
|
| タイトル |
The microRNA miR-71 suppresses maladaptive UPRmt signaling through both cell-autonomous and cell-non-autonomous mechanisms.
|
| ジャーナル |
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.
|
| 巻・号 |
17(1)
|
| ページ |
510
|
| 公開日 |
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
|
| リソース情報 |
| 線虫 |
tm4525
tm12973
tm4803 |
