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Biology subjects

Lesnik, C.

Publications and source records attributed to Lesnik, C..

2 recordsLinked to original sources

Enhanced Branched-Chain Amino Acid Metabolism Improves Age-related Reproductive Function

Reproductive aging is one of the earliest human aging 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 C. 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. Importantly, 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.

cell biology↗

Horizontal and vertical transmission of transgenerational memories via the Cer1 transposon

Animals face both external and internal dangers: pathogens threaten from the environment, and unstable genomic elements threaten from within. Previously, we discovered that C. elegans protects itself from pathogens by "reading" bacterial small RNAs and using this information to both induce avoidance and transmit memories for several generations. Here we found that these memories can be transferred to naive animals via Cer1 retrotransposon-encoded capsids. Cer1 functions at the step of transmission of information from the germline to neurons, and is required for C. elegans learned avoidance ability and for mothers to pass this information on to progeny. The presence of the Cer1 retrotransposon in wild C. elegans strains correlates with the ability to learn and inherit small RNA-induced pathogen avoidance. Together, these results suggest that C. elegans has co-opted a potentially dangerous retrotransposon to instead protect itself and its progeny from a common pathogen through its inter-tissue signaling ability, hijacking this genomic element for its own adaptive immunity benefit.

genetics↗