GSE121920
Loss of mitochondrial proline catabolism depletes FAD, impairing sperm function, and male reproductive advantage
Exposure to environmental stress has a clinically established influence on male reproductive health, but the impact of normal cellular metabolism on sperm quality and function is less well-defined.  Here we show that homeostatic changes in mitochondrial dynamics driven by defective mitochondrial proline catabolism result in pleiotropic consequences on sperm quality and competitive fitness. Disruption of alh-6, which converts 1-pyrroline-5-carboxylate (P5C) to glutamate, results in P5C accumulation that drives oxidative stress, activation of the cytoprotective transcription factor SKN-1, and a reduction of energy-storing flavin adenine dinucleotide (FAD) levels. These molecular changes lead to premature male reproductive senescence by reducing sperm quality.  These sperm-specific defects are suppressed by abating P5C metabolism, by treatment with antioxidants to combat reactive oxygen species (ROS), or by feeding diets that restore FAD levels. Our results define a role for mitochondrial proline catabolism and FAD homeostasis on sperm function and specify strategies to pharmacologically reverse unintended outcomes from SKN-1/Nrf transcriptional activation. Overall design: Our study aim to look at transcriptional signatures that define the physiological changes in alh-6 mutant animals as young and old animals. 12 RNA samples in total are turned in for high-throughput sequencing. N2 (WT) and lax105 (alh-6) worms are collected in triplicates at two time points: L4 and day 3 adults.