RT Journal Article
SR Electronic
T1 Enhanced Branched-Chain Amino Acid Metabolism Improves Age-related Reproductive Function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.09.527915
DO 10.1101/2023.02.09.527915
A1 Chen Lesnik
A1 Salman Sohrabi
A1 Jasmine M. Ashraf
A1 Rachel Kaletsky
A1 Vanessa Cota
A1 Titas Sengupta
A1 William Keyes
A1 Coleen T. Murphy
YR 2023
UL http://biorxiv.org/content/early/2023/02/10/2023.02.09.527915.abstract
AB Reproductive aging is one of the earliest aging phenotypes, and mitochondrial dysfunction has been linked to a decline in oocyte quality. However, the mitochondria-related processes that are critical for oocyte quality maintenance with age have not been fully identified. We isolated mitochondria from young and aged wild-type and long-reproductive daf-2 mutant C. elegans for proteomic analysis. We found that the mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and are distinct from mitochondrial proteins of aged wild-type animals. The first enzyme of the branched-chain amino acid (BCAA) metabolism pathway, BCAT-1, is more abundant in young and daf-2 mitochondria. Upon knockdown of bcat-1 in daf-2, reproduction is shortened, mitochondrial ROS levels are elevated, and mitochondria shift to a perinuclear distribution within the mature oocytes. Moreover, bcat-1 knockdown decreases daf-2 oocyte quality and reduces reproductive capability in late age, indicating the importance of this pathway in the maintenance of oocyte quality with age. Importantly, we can extend reproduction in wild-type animals both by bcat-1 overexpression and by supplementing vitamin B1, a cofactor needed for the BCAA metabolism.HighlightsBCAT-1 is abundant in mitochondria isolated from young wild-type worms and the long-lived mutant daf-2.Downregulating bcat-1 in daf-2 mutants reduces daf-2 reproductive span, alters mitochondrial oocyte distribution, and elevates mtROS in mature oocytes.Overexpression of bcat-1 extends reproductive capability.Supplementation with thiamine (vitamin B1) extends reproductive capability.Competing Interest StatementThe authors have declared no competing interest.