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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/51601 |
| _version_ | 1818026521149833216 |
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| author | Grigor Varuzhanyan Rebecca Rojansky Michael J Sweredoski Robert LJ Graham Sonja Hess Mark S Ladinsky David C Chan |
| author_facet | Grigor Varuzhanyan Rebecca Rojansky Michael J Sweredoski Robert LJ Graham Sonja Hess Mark S Ladinsky David C Chan |
| author_sort | Grigor Varuzhanyan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T04:33:19Z |
| format | Article |
| id | doaj.art-bea96b69c3024295bb0ecb0861f2d75c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:33:19Z |
| publishDate | 2019-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bea96b69c3024295bb0ecb0861f2d75c2022-12-22T02:02:04ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.51601Mitochondrial fusion is required for spermatogonial differentiation and meiosisGrigor Varuzhanyan0https://orcid.org/0000-0001-6165-0857Rebecca Rojansky1Michael J Sweredoski2https://orcid.org/0000-0003-0878-3831Robert LJ Graham3Sonja Hess4Mark S Ladinsky5David C Chan6https://orcid.org/0000-0002-0191-2154Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesProteome Exploration Laboratory of the Beckman Institute, California Institute of Technology, Pasadena, United StatesProteome Exploration Laboratory of the Beckman Institute, California Institute of Technology, Pasadena, United StatesProteome Exploration Laboratory of the Beckman Institute, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDifferentiating 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.https://elifesciences.org/articles/51601mitochondriametabolismmembrane fusionspermatogenesis |
| spellingShingle | Grigor Varuzhanyan Rebecca Rojansky Michael J Sweredoski Robert LJ Graham Sonja Hess Mark S Ladinsky David C Chan Mitochondrial fusion is required for spermatogonial differentiation and meiosis eLife mitochondria metabolism membrane fusion spermatogenesis |
| 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 | mitochondria metabolism membrane fusion spermatogenesis |
| url | https://elifesciences.org/articles/51601 |
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