|
| Status |
Public on Feb 17, 2020 |
| Title |
Loss of mitochondrial proline catabolism depletes FAD, impairing sperm function, and male reproductive advantage |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
|
| |
|
| Contributor(s) |
Yen C, Curran S |
| Citation(s) |
32022684 |
| Submission date |
Oct 29, 2018 |
| Last update date |
Mar 03, 2020 |
| Contact name |
Sean Curran |
| E-mail(s) |
spcurran@usc.edu
|
| Organization name |
University of Southern California
|
| Department |
Davis School of Gerontology
|
| Lab |
Curran
|
| Street address |
3715 McClintock Ave
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90089 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13657 |
Illumina HiSeq 2000 (Caenorhabditis elegans) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA499069 |
| SRA |
SRP167129 |
Less...
More...