{"doi":"10.7554/elife.52899","title":"Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans","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.","journal":"eLife","year":2020,"id":91315,"datarank":1.2798124312495727,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.7055162217762082,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.7055162217762082,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":29,"citers_with_citation_signal":20,"citers_with_endowment":20,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE121920"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458170,"name":"Dana L. Ruter","orcid":null,"position":1,"is_corresponding":false},{"id":458171,"name":"Christian D. Turner","orcid":null,"position":2,"is_corresponding":false},{"id":332241,"name":"Shanshan Pang","orcid":"0000-0002-7872-1524","position":3,"is_corresponding":false},{"id":277109,"name":"Sean P. Curran","orcid":"0000-0001-7791-6453","position":4,"is_corresponding":false},{"id":458169,"name":"Chia‐An Yen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T22:28:45.409789Z","pmid":"32022684","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}