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  • Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans.

Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans.

eLife (2020-02-06)
Chia-An Yen, Dana L Ruter, Christian D Turner, Shanshan Pang, Sean P Curran
RESUMO

Exposure to environmental stress is clinically established to influence male reproductive health, but the impact of normal cellular metabolism on sperm quality is less well-defined. Here we show that impaired mitochondrial proline catabolism, reduces energy-storing flavin adenine dinucleotide (FAD) levels, alters mitochondrial dynamics toward fusion, and leads to age-related loss of sperm quality (size and activity), which diminishes competitive fitness of the animal. Loss of the 1-pyrroline-5-carboxylate dehydrogenase enzyme alh-6 that catalyzes the second step in mitochondrial proline catabolism leads to premature male reproductive senescence. Reducing the expression of the proline catabolism enzyme alh-6 or FAD biosynthesis pathway genes in the germline is sufficient to recapitulate the sperm-related phenotypes observed in alh-6 loss-of-function mutants. These sperm-specific defects are suppressed by feeding diets that restore FAD levels. Our results define a cell autonomous role for mitochondrial proline catabolism and FAD homeostasis on sperm function and specify strategies to pharmacologically reverse these defects.

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Sigma-Aldrich
(−)-Riboflavin, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98%
Sigma-Aldrich
Protease from Streptomyces griseus, powder, BioReagent, suitable for mouse embryo cell culture, ≥3.5 units/mg solid