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000282567 1001_ $$0P:(DE-2719)9001754$$aMondal, Mrityunjoy$$b0$$eFirst author$$udzne
000282567 245__ $$aDietary lipid content modifies wah-1/AIFM1-associated phenotypes via LRK-1 and DRP-1 expression in C. elegans.
000282567 260__ $$a[London]$$bSpringer Nature$$c2025
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000282567 520__ $$aEukaryotic 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.
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000282567 650_7 $$2NLM Chemicals$$aCaenorhabditis elegans Proteins
000282567 650_7 $$2NLM Chemicals$$aDietary Fats
000282567 650_7 $$0EC 3.6.5.5$$2NLM Chemicals$$aDynamins
000282567 650_7 $$0EC 3.6.5.5$$2NLM Chemicals$$adynamin-related protein 1, C elegans
000282567 650_2 $$2MeSH$$aAnimals
000282567 650_2 $$2MeSH$$aCaenorhabditis elegans: metabolism
000282567 650_2 $$2MeSH$$aCaenorhabditis elegans: genetics
000282567 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: metabolism
000282567 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: genetics
000282567 650_2 $$2MeSH$$aPhenotype
000282567 650_2 $$2MeSH$$aDietary Fats: metabolism
000282567 650_2 $$2MeSH$$aDietary Fats: pharmacology
000282567 650_2 $$2MeSH$$aMitochondria: metabolism
000282567 650_2 $$2MeSH$$aDynamins: metabolism
000282567 650_2 $$2MeSH$$aDynamins: genetics
000282567 650_2 $$2MeSH$$aMutation
000282567 650_2 $$2MeSH$$aLongevity
000282567 650_2 $$2MeSH$$aAutophagy
000282567 7001_ $$0P:(DE-2719)2812562$$aScifo, Enzo$$b1
000282567 7001_ $$0P:(DE-2719)9002528$$aCiliberti, Rossella Erminia$$b2$$udzne
000282567 7001_ $$0P:(DE-2719)2811527$$aWischhof, Lena$$b3$$udzne
000282567 7001_ $$00009-0003-0980-8639$$aAbbariki, Tannaz Norizadeh$$b4
000282567 7001_ $$0P:(DE-2719)2814190$$aJackson, Joshua$$b5
000282567 7001_ $$0P:(DE-2719)9002833$$aMenegatou, Ioanna-Maria$$b6$$udzne
000282567 7001_ $$aZeisler-Diehl, Viktoria$$b7
000282567 7001_ $$aRiemer, Jan$$b8
000282567 7001_ $$00000-0001-9764-0482$$aJussila, Benjamin$$b9
000282567 7001_ $$aHopkins, Christopher E$$b10
000282567 7001_ $$00000-0002-4736-9222$$aKierszniowska, Sylwia$$b11
000282567 7001_ $$00000-0001-7003-9929$$aSchreiber, Lukas$$b12
000282567 7001_ $$0P:(DE-2719)2010732$$aNicotera, Pierluigi$$b13$$udzne
000282567 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b14
000282567 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b15$$eLast author
000282567 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-66900-8$$gVol. 16, no. 1, p. 10817$$n1$$p10817$$tNature Communications$$v16$$x2041-1723$$y2025
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