| RRC ID |
87974
|
| Author |
Yang X, Wei R, Meng F, Liu D, Gong X, Ruvkun G, Wei W.
|
| Title |
Mitochondrial fission surveillance is coupled to Caenorhabditis elegans DNA and chromosome segregation integrity.
|
| Journal |
PLoS Genet
|
| Abstract |
Mitochondrial fission and fusion are tightly regulated to specify mitochondrial abundance, localization, and arrangement during cell division as well as in the diverse differentiated cell types and physiological states. However, the regulatory pathways for such mitochondrial dynamics are less explored than the mitochondrial fission and fusion components. Here we report a large-scale screen for genes that regulate mitochondrial fission. Mitochondrial fission defects cause a characteristic uneven fluorescent pattern in embryos carrying mitochondrial stress reporter genes. Using this uneven activation, we performed RNAi screens that identified 3 kinase genes from a ~ 500-kinase library and another 11 genes from 3,300 random genes that function in mitochondrial fission. Many of these identified genes play roles in chromosome segregation. We found that chromosome missegregation and genome instability lead to dysregulation of mitochondrial fission, possibly independent of DRP-1. ATL-1, the C. elegans ATR orthologue, plays a potentially protective role in alleviating the mitochondrial fission defect caused by chromosome missegregation. This establishes a screening paradigm for identifying mitochondrial fission regulators, which reveals the potential role of ATR in surveilling mitochondrial fission to mitigate dysregulation caused by improper chromosome segregation.
|
| Volume |
21(4)
|
| Pages |
e1011678
|
| Published |
2025-4-1
|
| DOI |
10.1371/journal.pgen.1011678
|
| PII |
PGENETICS-D-24-01151
|
| PMID |
40279356
|
| PMC |
PMC12064022
|
| MeSH |
Animals
Caenorhabditis elegans* / genetics
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Chromosome Segregation* / genetics
DNA, Mitochondrial / genetics
Genomic Instability
Mitochondria* / genetics
Mitochondria* / metabolism
Mitochondrial Dynamics* / genetics
RNA Interference
|
| Resource |
| C.elegans |
tm1108
tm1502
tm2395
tm7587
tm1867
tm1832
tm3041 |
