| RRC ID |
88144
|
| 著者 |
Mondal M, Scifo E, Ciliberti RE, Wischhof L, Abbariki TN, Jackson J, Menegatou IM, Zeisler-Diehl V, Riemer J, Jussila B, Hopkins CE, Kierszniowska S, Schreiber L, Nicotera P, Ehninger D, Bano D.
|
| タイトル |
Dietary lipid content modifies wah-1/AIFM1-associated phenotypes via LRK-1 and DRP-1 expression in C. elegans.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Eukaryotic cells rely on mitochondria to fine-tune their metabolism in response to environmental and nutritional changes. However, how mitochondria adapt to nutrient availability and how diets impact mitochondrial disease progression, remain unclear. Here, we show that lipid-derived diets influence the survival of Caenorhabditis elegans carrying a hypomorphic wah-1/AIFM1 mutation that compromises mitochondrial Complex I assembly. Comparative proteomic and lipidomic analyses reveal that the overall metabolic profile of wah-1/AIFM1 mutants varies with bacterial diet. Specifically, high-lipid diets extend lifespan by promoting mitochondrial network maintenance and lipid accumulation, whereas low-lipid diets shorten animal survival via overactivation of LRK-1 and DRP-1. We demonstrate that LRK-1 inhibition downregulates DRP-1 expression, reduces mitochondrial network fragmentation, and attenuates excessive autophagy, thereby rescuing the survival defects of wah-1 mutants maintained on low-lipid diets. Together, these findings suggest that nutrition, and particularly lipid intake, may ameliorate certain disease phenotypes associated with an inherited mutation that disrupts mitochondrial bioenergetics.
|
| 巻・号 |
16(1)
|
| ページ |
10817
|
| 公開日 |
2025-12-1
|
| DOI |
10.1038/s41467-025-66900-8
|
| PII |
10.1038/s41467-025-66900-8
|
| PMID |
41326385
|
| PMC |
PMC12669733
|
| MeSH |
Animals
Autophagy
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Dietary Fats* / metabolism
Dietary Fats* / pharmacology
Dynamins* / genetics
Dynamins* / metabolism
Longevity
Mitochondria / metabolism
Mutation
Phenotype
|
| リソース情報 |
| 線虫 |
tm1108
tm4525 |
