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Mitochondrial fusion is required for spermatogonial differentiation and meiosis
Differentiating cells tailor their metabolism to fulfill their specialized functions. We examined whether mitochondrial fusion is important for metabolic tailoring during spermatogenesis. Acutely after depletion of mitofusins Mfn1 and Mfn2, spermatogenesis arrests due to failure to accomplish a meta...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805159/ https://www.ncbi.nlm.nih.gov/pubmed/31596236 http://dx.doi.org/10.7554/eLife.51601 |
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author | Varuzhanyan, Grigor Rojansky, Rebecca Sweredoski, Michael J Graham, Robert LJ Hess, Sonja Ladinsky, Mark S Chan, David C |
author_facet | Varuzhanyan, Grigor Rojansky, Rebecca Sweredoski, Michael J Graham, Robert LJ Hess, Sonja Ladinsky, Mark S Chan, David C |
author_sort | Varuzhanyan, Grigor |
collection | PubMed |
description | Differentiating cells tailor their metabolism to fulfill their specialized functions. We examined whether mitochondrial fusion is important for metabolic tailoring during spermatogenesis. Acutely after depletion of mitofusins Mfn1 and Mfn2, spermatogenesis arrests due to failure to accomplish a metabolic shift during meiosis. This metabolic shift includes increased mitochondrial content, mitochondrial elongation, and upregulation of oxidative phosphorylation (OXPHOS). With long-term mitofusin loss, all differentiating germ cell types are depleted, but proliferation of stem-like undifferentiated spermatogonia remains unaffected. Thus, compared with undifferentiated spermatogonia, differentiating spermatogonia and meiotic spermatocytes have cell physiologies that require high levels of mitochondrial fusion. Proteomics in fibroblasts reveals that mitofusin-null cells downregulate respiratory chain complexes and mitochondrial ribosomal subunits. Similarly, mitofusin depletion in immortalized spermatocytes or germ cells in vivo results in reduced OXPHOS subunits and activity. We reveal that by promoting OXPHOS, mitofusins enable spermatogonial differentiation and a metabolic shift during meiosis. |
format | Online Article Text |
id | pubmed-6805159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-68051592019-10-24 Mitochondrial fusion is required for spermatogonial differentiation and meiosis Varuzhanyan, Grigor Rojansky, Rebecca Sweredoski, Michael J Graham, Robert LJ Hess, Sonja Ladinsky, Mark S Chan, David C eLife Cell Biology Differentiating cells tailor their metabolism to fulfill their specialized functions. We examined whether mitochondrial fusion is important for metabolic tailoring during spermatogenesis. Acutely after depletion of mitofusins Mfn1 and Mfn2, spermatogenesis arrests due to failure to accomplish a metabolic shift during meiosis. This metabolic shift includes increased mitochondrial content, mitochondrial elongation, and upregulation of oxidative phosphorylation (OXPHOS). With long-term mitofusin loss, all differentiating germ cell types are depleted, but proliferation of stem-like undifferentiated spermatogonia remains unaffected. Thus, compared with undifferentiated spermatogonia, differentiating spermatogonia and meiotic spermatocytes have cell physiologies that require high levels of mitochondrial fusion. Proteomics in fibroblasts reveals that mitofusin-null cells downregulate respiratory chain complexes and mitochondrial ribosomal subunits. Similarly, mitofusin depletion in immortalized spermatocytes or germ cells in vivo results in reduced OXPHOS subunits and activity. We reveal that by promoting OXPHOS, mitofusins enable spermatogonial differentiation and a metabolic shift during meiosis. eLife Sciences Publications, Ltd 2019-10-09 /pmc/articles/PMC6805159/ /pubmed/31596236 http://dx.doi.org/10.7554/eLife.51601 Text en © 2019, Varuzhanyan et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Varuzhanyan, Grigor Rojansky, Rebecca Sweredoski, Michael J Graham, Robert LJ Hess, Sonja Ladinsky, Mark S Chan, David C Mitochondrial fusion is required for spermatogonial differentiation and meiosis |
title | Mitochondrial fusion is required for spermatogonial differentiation and meiosis |
title_full | Mitochondrial fusion is required for spermatogonial differentiation and meiosis |
title_fullStr | Mitochondrial fusion is required for spermatogonial differentiation and meiosis |
title_full_unstemmed | Mitochondrial fusion is required for spermatogonial differentiation and meiosis |
title_short | Mitochondrial fusion is required for spermatogonial differentiation and meiosis |
title_sort | mitochondrial fusion is required for spermatogonial differentiation and meiosis |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805159/ https://www.ncbi.nlm.nih.gov/pubmed/31596236 http://dx.doi.org/10.7554/eLife.51601 |
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