Journal Article

DZNE-2025-01330

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dietary lipid content modifies wah-1/AIFM1-associated phenotypes via LRK-1 and DRP-1 expression in C. elegans.

Mondal, M. (First author)DZNE* ; Scifo, E.DZNE* ; Ciliberti, R. E.DZNE* ; Wischhof, L.DZNE* ; Abbariki, T. N.DZNE* ; Jackson, J.DZNE* ; Menegatou, I.-M.DZNE* ; Zeisler-Diehl, V. ; Riemer, J. ; Jussila, B. ; Hopkins, C. E. ; Kierszniowska, S. ; Schreiber, L. ; Nicotera, P.DZNE* ; Ehninger, D.DZNE* ; Bano, D. (Last author)DZNE*

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-025-66900-8

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.

Keyword(s): Animals (MeSH) ; Caenorhabditis elegans: metabolism (MeSH) ; Caenorhabditis elegans: genetics (MeSH) ; Caenorhabditis elegans Proteins: metabolism (MeSH) ; Caenorhabditis elegans Proteins: genetics (MeSH) ; Phenotype (MeSH) ; Dietary Fats: metabolism (MeSH) ; Dietary Fats: pharmacology (MeSH) ; Mitochondria: metabolism (MeSH) ; Dynamins: metabolism (MeSH) ; Dynamins: genetics (MeSH) ; Mutation (MeSH) ; Longevity (MeSH) ; Autophagy (MeSH) ; Caenorhabditis elegans Proteins ; Dietary Fats ; Dynamins ; dynamin-related protein 1, C elegans

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Contributing Institute(s):

1. Aging and Neurodegeneration (AG Bano)
2. Translational Biogerontology (AG Ehninger)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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