RRC ID 59627
Author Yen CA, Ruter DL, Turner CD, Pang S, Curran SP.
Title Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans.
Journal 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.
Volume 9
Published 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
Times Cited 0
C.elegans tm1108 tm1301