TY  - JOUR
AU  - Mondal, Mrityunjoy
AU  - Scifo, Enzo
AU  - Ciliberti, Rossella Erminia
AU  - Wischhof, Lena
AU  - Abbariki, Tannaz Norizadeh
AU  - Jackson, Joshua
AU  - Menegatou, Ioanna-Maria
AU  - Zeisler-Diehl, Viktoria
AU  - Riemer, Jan
AU  - Jussila, Benjamin
AU  - Hopkins, Christopher E
AU  - Kierszniowska, Sylwia
AU  - Schreiber, Lukas
AU  - Nicotera, Pierluigi
AU  - Ehninger, Dan
AU  - Bano, Daniele
TI  - Dietary lipid content modifies wah-1/AIFM1-associated phenotypes via LRK-1 and DRP-1 expression in C. elegans.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-01330
SP  - 10817
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Caenorhabditis elegans: metabolism
KW  - Caenorhabditis elegans: genetics
KW  - Caenorhabditis elegans Proteins: metabolism
KW  - Caenorhabditis elegans Proteins: genetics
KW  - Phenotype
KW  - Dietary Fats: metabolism
KW  - Dietary Fats: pharmacology
KW  - Mitochondria: metabolism
KW  - Dynamins: metabolism
KW  - Dynamins: genetics
KW  - Mutation
KW  - Longevity
KW  - Autophagy
KW  - Caenorhabditis elegans Proteins (NLM Chemicals)
KW  - Dietary Fats (NLM Chemicals)
KW  - Dynamins (NLM Chemicals)
KW  - dynamin-related protein 1, C elegans (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41326385
DO  - DOI:10.1038/s41467-025-66900-8
UR  - https://pub.dzne.de/record/282567
ER  -