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Mitochondrial fission factor (Mff) is required for organization of the mitochondrial sheath in spermatids

Varuzhanyan, Grigor and Chen, Hsiuchen and Rojansky, Rebecca and Ladinsky, Mark S. and McCaffery, J. Michael and Chan, David C. (2021) Mitochondrial fission factor (Mff) is required for organization of the mitochondrial sheath in spermatids. Biochimica et Biophysica Acta - General Subjects, 1865 (5). Art. No. 129845. ISSN 0304-4165. https://resolver.caltech.edu/CaltechAUTHORS:20210119-143306934

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[img] Video (MPEG) (Video 1. EM tomogram and 3D rendering of longitudinal section of sperm from WT caudal epididymis) - Supplemental Material
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[img] Video (MPEG) (Video 2. EM tomogram and 3D rendering of longitudinal section of sperm from Mffgt caudal epididymis) - Supplemental Material
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[img] Video (MPEG) (Video 3. EM tomogram and 3D rendering of transverse section of sperm from WT caudal epididymis) - Supplemental Material
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[img] Video (MPEG) (Video 4. EM tomogram and 3D rendering of transverse section of sperm from Mffgt caudal epididymis) - Supplemental Material
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[img] Video (MPEG) (Video 5. Movie of sperm isolated from caudal epididymides of a WT mouse) - Supplemental Material
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[img] Video (MPEG) (Video 6. Movie of sperm isolated from caudal epididymides of an Mffgt mouse) - Supplemental Material
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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.bbagen.2021.129845DOIArticle
ORCID:
AuthorORCID
Varuzhanyan, Grigor0000-0001-6165-0857
Ladinsky, Mark S.0000-0002-1036-3513
Chan, David C.0000-0002-0191-2154
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.
Group:Kavli Nanoscience Institute
Funders:
Funding AgencyGrant Number
NIHR35 GM127147
NSF Graduate Research FellowshipDGE-1144469
NIH Predoctoral FellowshipGM07616T32
NIH2 P50 AI150464
Subject Keywords:Mitochondrial fission; Spermatogenesis; Mitochondrial sheath
Issue or Number:5
Record Number:CaltechAUTHORS:20210119-143306934
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210119-143306934
Official Citation:Grigor Varuzhanyan, Hsiuchen Chen, Rebecca Rojansky, Mark S. Ladinsky, J. Michael McCaffery, David C. Chan, Mitochondrial fission factor (Mff) is required for organization of the mitochondrial sheath in spermatids, Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1865, Issue 5, 2021, 129845, ISSN 0304-4165, https://doi.org/10.1016/j.bbagen.2021.129845. (http://www.sciencedirect.com/science/article/pii/S0304416521000040)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107554
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:20 Jan 2021 15:50
Last Modified:26 Jan 2021 18:53

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