SPELL - Nematode

Citation	Lesnik C, Kaletsky R, Ashraf JM, Sohrabi S, Cota V, SenGupta T, Keyes W, Luo S, Murphy CT. Enhanced branched-chain amino acid metabolism improves age-related reproduction in C. elegans. Nat Metab, 2024.
PubMed ID	38418585
Short Description	Enhanced branched-chain amino acid metabolism improves age-related reproduction in C. elegans. GEO Record: N.A. Platform: N.A. Download gene-centric, log2 transformed data: WBPaper00066547.ce.ms.csv
# of Conditions	12
Full Description	Reproductive ageing is one of the earliest human ageing phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline; however, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to Caenorhabditis elegans oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive daf-2 mutants. Here we show that the mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes. Reduction of the BCAA catabolism enzyme BCAT-1 shortens reproduction, elevates mitochondrial reactive oxygen species levels, and shifts mitochondrial localization. Moreover, bcat-1 knockdown decreases oocyte quality in daf-2 worms and reduces reproductive capability, indicating the role of this pathway in the maintenance of oocyte quality with age. Notably, oocyte quality deterioration can be delayed, and reproduction can be extended in wild-type animals both by bcat-1 overexpression and by supplementing with vitamin B1, a cofactor needed for BCAA metabolism. Experimental Details: MassSpec_WBPaper00066547:daf-2(e1370)_day1_repI MassSpec_WBPaper00066547:daf-2(e1370)_day1_repII MassSpec_WBPaper00066547:daf-2(e1370)_day1_repIII MassSpec_WBPaper00066547:daf-2(e1370)_day5_repI MassSpec_WBPaper00066547:daf-2(e1370)_day5_repII MassSpec_WBPaper00066547:daf-2(e1370)_day5_repIII MassSpec_WBPaper00066547:N2_day1_repI MassSpec_WBPaper00066547:N2_day1_repII MassSpec_WBPaper00066547:N2_day1_repIII MassSpec_WBPaper00066547:N2_day5_repI MassSpec_WBPaper00066547:N2_day5_repII MassSpec_WBPaper00066547:N2_day5_repIII.
Tags	Method: proteomics, Species: Caenorhabditis elegans, Topic: aging, Topic: WT vs. mutant