1. Cell Biology
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Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in C. elegans

  1. Chia-An Yen
  2. Dana L Ruter
  3. Christian D Turner
  4. Shanshan Pang
  5. Sean P Curran  Is a corresponding author
  1. University of Southern California, United States
  2. University of North Carolina, United States
  3. Chongqing University, China
Research Article
  • Cited 12
  • Views 1,292
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Cite this article as: eLife 2020;9:e52899 doi: 10.7554/eLife.52899

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.

Data availability

RNA-Seq data are deposited in GEO database (GSE121920).-

The following data sets were generated

Article and author information

Author details

  1. Chia-An Yen

    Gerontology; Molecular and Computational Biology; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Dana L Ruter

    Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Christian D Turner

    Gerontology; Molecular and Computational Biology; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Shanshan Pang

    School of Life Sciences, Chongqing University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Sean P Curran

    Gerontology; Molecular and Computational Biology; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, United States
    For correspondence
    spcurran@usc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7791-6453

Funding

National Institutes of Health (GM109028)

  • Sean P Curran

National Institutes of Health (AG058610)

  • Sean P Curran

National Institutes of Health (AG063947)

  • Sean P Curran

National Institutes of Health (AG000037)

  • Dana L Ruter

National Institutes of Health (GM118289)

  • Christian D Turner

American Federation for Aging Research

  • Chia-An Yen
  • Sean P Curran

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China

Publication history

  1. Received: October 19, 2019
  2. Accepted: February 5, 2020
  3. Accepted Manuscript published: February 5, 2020 (version 1)
  4. Version of Record published: February 20, 2020 (version 2)

Copyright

© 2020, Yen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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