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@ARTICLE{Mondal:282567,
author = {Mondal, Mrityunjoy and Scifo, Enzo and Ciliberti, Rossella
Erminia and Wischhof, Lena and Abbariki, Tannaz Norizadeh
and Jackson, Joshua and Menegatou, Ioanna-Maria and
Zeisler-Diehl, Viktoria and Riemer, Jan and Jussila,
Benjamin and Hopkins, Christopher E and Kierszniowska,
Sylwia and Schreiber, Lukas and Nicotera, Pierluigi and
Ehninger, Dan and Bano, Daniele},
title = {{D}ietary lipid content modifies wah-1/{AIFM}1-associated
phenotypes via {LRK}-1 and {DRP}-1 expression in {C}.
elegans.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DZNE-2025-01330},
pages = {10817},
year = {2025},
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.},
keywords = {Animals / Caenorhabditis elegans: metabolism /
Caenorhabditis elegans: genetics / Caenorhabditis elegans
Proteins: metabolism / Caenorhabditis elegans Proteins:
genetics / Phenotype / Dietary Fats: metabolism / Dietary
Fats: pharmacology / Mitochondria: metabolism / Dynamins:
metabolism / Dynamins: genetics / Mutation / Longevity /
Autophagy / Caenorhabditis elegans Proteins (NLM Chemicals)
/ Dietary Fats (NLM Chemicals) / Dynamins (NLM Chemicals) /
dynamin-related protein 1, C elegans (NLM Chemicals)},
cin = {AG Bano / AG Ehninger},
ddc = {500},
cid = {I:(DE-2719)1013003 / I:(DE-2719)1013005},
pnm = {351 - Brain Function (POF4-351) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41326385},
doi = {10.1038/s41467-025-66900-8},
url = {https://pub.dzne.de/record/282567},
}