| RRC ID |
80758
|
| 著者 |
Dai CY, Ng CC, Hung GCC, Kirmes I, Hughes LA, Du Y, Brosnan CA, Ahier A, Hahn A, Haynes CM, Rackham O, Filipovska A, Zuryn S.
|
| タイトル |
ATFS-1 counteracts mitochondrial DNA damage by promoting repair over transcription.
|
| ジャーナル |
Nat Cell Biol
|
| Abstract |
The ability to balance conflicting functional demands is critical for ensuring organismal survival. The transcription and repair of the mitochondrial genome (mtDNA) requires separate enzymatic activities that can sterically compete1, suggesting a life-long trade-off between these two processes. Here in Caenorhabditis elegans, we find that the bZIP transcription factor ATFS-1/Atf5 (refs. 2,3) regulates this balance in favour of mtDNA repair by localizing to mitochondria and interfering with the assembly of the mitochondrial pre-initiation transcription complex between HMG-5/TFAM and RPOM-1/mtRNAP. ATFS-1-mediated transcriptional inhibition decreases age-dependent mtDNA molecular damage through the DNA glycosylase NTH-1/NTH1, as well as the helicase TWNK-1/TWNK, resulting in an enhancement in the functional longevity of cells and protection against decline in animal behaviour caused by targeted and severe mtDNA damage. Together, our findings reveal that ATFS-1 acts as a molecular focal point for the control of balance between genome expression and maintenance in the mitochondria.
|
| 巻・号 |
25(8)
|
| ページ |
1111-1120
|
| 公開日 |
2023-8-1
|
| DOI |
10.1038/s41556-023-01192-y
|
| PII |
10.1038/s41556-023-01192-y
|
| PMID |
37460695
|
| MeSH |
Animals
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Cyclic AMP Response Element-Binding Protein / genetics
DNA Damage
DNA, Mitochondrial* / genetics
DNA, Mitochondrial* / metabolism
Mitochondria / genetics
Mitochondria / metabolism
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
|
| リソース情報 |
| 線虫 |
tm4525
tm4919 |
