Mitochondrial succinate dehydrogenase function is essential for sperm motility and male fertility

Rachel M Woodhouse; Natalya Frolows; Guoqiang Wang; Azelle Hawdon; Edmund Heng Kin Wong; Linda C Dansereau; Yingying Su; Liam D Adair; Elizabeth J New; Ashleigh M Philp; Wei Kang Tan; Andrew Philp; Alyson Ashe

doi:10.1016/j.isci.2022.105573

Mitochondrial succinate dehydrogenase function is essential for sperm motility and male fertility

iScience. 2022 Nov 14;25(12):105573. doi: 10.1016/j.isci.2022.105573. eCollection 2022 Dec 22.

Authors

Rachel M Woodhouse^{1

2}, Natalya Frolows^{1

3}, Guoqiang Wang⁴, Azelle Hawdon^{1

5}, Edmund Heng Kin Wong¹, Linda C Dansereau^{6

7}, Yingying Su⁸, Liam D Adair^{9

10}, Elizabeth J New^{9

10}, Ashleigh M Philp⁷, Wei Kang Tan¹, Andrew Philp^{11

12}, Alyson Ashe¹

Affiliations

¹ The University of Sydney, School of Life and Environmental Sciences, Sydney, NSW 2006, Australia.
² Division of Genome Science and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.
³ CSIRO Health and Biosecurity, Sydney, NSW 2113, Australia.
⁴ Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
⁵ Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia.
⁶ Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁷ St Vincent's Clinical School, UNSW Medicine, University of NSW, Sydney, NSW 2010, Australia.
⁸ Sydney Microscopy and Microanalysis, The University of Sydney, Sydney, NSW 2006, Australia.
⁹ The University of Sydney, School of Chemistry, Sydney, NSW 2006, Australia.
¹⁰ Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, NSW 2006, Australia.
¹¹ Centre for Healthy Ageing, Centenary Institute, Missenden Road, Sydney, NSW 2050, Australia.
¹² Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, NSW 2006, Australia.

Abstract

Mitochondrial health is crucial to sperm quality and male fertility, but the precise role of mitochondria in sperm function remains unclear. SDHA is a component of the succinate dehydrogenase (SDH) complex and plays a critical role in mitochondria. In humans, SDH activity is positively correlated with sperm quality, and mutations in SDHA are associated with Leigh Syndrome. Here we report that the C. elegans SDHA orthologue SDHA-2 is essential for male fertility: sdha-2 mutants produce dramatically fewer offspring due to defective sperm activation and motility, have hyperfused sperm mitochondria, and disrupted redox balance. Similar sperm motility defects in sdha-1 and icl-1 mutant animals suggest an imbalance in metabolites may underlie the fertility defect. Our results demonstrate a role for SDHA-2 in sperm motility and male reproductive health and establish an animal model of SDH deficiency-associated infertility.

Keywords: Biological sciences; biochemistry; cell biology; molecular biology.

Grants and funding

P40 OD010440/OD/NIH HHS/United States