論文 - 詳細
| RRC ID | 59627 |
|---|---|
| 著者 | Yen CA, Ruter DL, Turner CD, Pang S, Curran SP. |
| タイトル | Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans. |
| ジャーナル | Elife |
| Abstract |
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. |
| 巻・号 | 9 |
| 公開日 | 2020-2-5 |
| DOI | 10.7554/eLife.52899 |
| PII | 52899 |
| PMID | 32022684 |
| PMC | PMC7032928 |
| MeSH | 1-Pyrroline-5-Carboxylate Dehydrogenase / genetics Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Flavin-Adenine Dinucleotide / metabolism* Male Mitochondria / enzymology Mitochondrial Dynamics Reproduction Spermatozoa / metabolism Spermatozoa / physiology* |
| IF | 7.551 |
| 引用数 | 0 |
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| 最多言及媒体 | News |
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| 線虫 | tm1108 tm1301 |