Enhanced branched-chain amino acid metabolism improves age-related reproduction in C. elegans

Chen Lesnik, Rachel Kaletsky, Jasmine M. Ashraf, Salman Sohrabi, Vanessa Cota, Titas Sengupta, William Keyes, Shijing Luo, Coleen T. Murphy

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Number of pages17
JournalNature Metabolism
Early online date28 Feb 2024
DOIs
StatePublished - Apr 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2024.

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Cell Biology

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