Mitochondrial fission factor (Mff) is required for organization of the mitochondrial sheath in spermatids
Abstract
Background: Mitochondrial fission counterbalances fusion to maintain organelle morphology, but its role during development remains poorly characterized. Mammalian spermatogenesis is a complex developmental process involving several drastic changes to mitochondrial shape and organization. Mitochondria are generally small and spherical in spermatogonia, elongate during meiosis, and fragment in haploid round spermatids. Near the end of spermatid maturation, small mitochondrial spheres line the axoneme, elongate, and tightly wrap around the midpiece to form the mitochondrial sheath, which is critical for fueling flagellar movements. It remains unclear how these changes in mitochondrial morphology are regulated and how they affect sperm development. Methods: We used genetic ablation of Mff (mitochondrial fission factor) in mice to investigate the role of mitochondrial fission during mammalian spermatogenesis. Results: Our analysis indicates that Mff is required for mitochondrial fragmentation in haploid round spermatids and for organizing mitochondria in the midpiece in elongating spermatids. In Mff mutant mice, round spermatids have aberrantly elongated mitochondria that often show central constrictions, suggestive of failed fission events. In elongating spermatids and spermatozoa, mitochondrial sheaths are disjointed, containing swollen mitochondria with large gaps between organelles. These mitochondrial abnormalities in Mff mutant sperm are associated with reduced respiratory chain Complex IV activity, aberrant sperm morphology and motility, and reduced fertility. Conclusions: Mff is required for organization of the mitochondrial sheath in mouse sperm. General Significance: Mitochondrial fission plays an important role in regulating mitochondrial organization during a complex developmental process.
Additional Information
© 2021 Elsevier. Received 23 June 2020, Revised 4 January 2021, Accepted 6 January 2021, Available online 19 January 2021. We thank all members of the Chan Lab for helpful discussions. We thank the Caltech Kavli Nanoscience Institute for maintenance of the TF-30 electron microscope. This work was supported by the National Institutes of Health (R35 GM127147). Grigor Varuzhanyan was supported by a National Science Foundation Graduate Research Fellowship (DGE-1144469) and a National Institutes of Health Cell and Molecular Biology Training Grant (GM07616T32). Mark S. Ladinsky was supported by the National Institute of Allergy and Infectious Diseases (NIAID) (2 P50 AI150464) (awarded to Pamela J. Bjorkman, Caltech). Credit author statement: Grigor Varuzhanyan:. Hsiuchen Chen:. Rebecca Rojansky:. Mark S Ladinsky: Investigation. J. Michael McCaffery: Investigation. David C. Chan:. The authors declare no competing interests.Attached Files
Accepted Version - nihms-1664330.pdf
Supplemental Material - 1-s2.0-S0304416521000040-mmc1_lrg.jpg
Supplemental Material - 1-s2.0-S0304416521000040-mmc2.mp4
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Supplemental Material - 1-s2.0-S0304416521000040-mmc6.mp4
Supplemental Material - 1-s2.0-S0304416521000040-mmc7.mp4
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Additional details
- PMCID
- PMC7904653
- Eprint ID
- 107554
- Resolver ID
- CaltechAUTHORS:20210119-143306934
- NIH
- R35 GM127147
- NSF Graduate Research Fellowship
- DGE-1144469
- NIH Predoctoral Fellowship
- GM07616T32
- NIH
- 2 P50 AI150464
- Created
-
2021-01-20Created from EPrint's datestamp field
- Updated
-
2022-05-09Created from EPrint's last_modified field
- Caltech groups
- Kavli Nanoscience Institute, Division of Biology and Biological Engineering