TY - JOUR TI - Mitochondrial fusion is required for spermatogonial differentiation and meiosis AU - Varuzhanyan, Grigor AU - Rojansky, Rebecca AU - Sweredoski, Michael J AU - Graham, Robert LJ AU - Hess, Sonja AU - Ladinsky, Mark S AU - Chan, David C A2 - Akhmanova, Anna A2 - Przedborski, Serge A2 - Przedborski, Serge A2 - Endo, Tsutomu A2 - Picard, Martin VL - 8 PY - 2019 DA - 2019/10/09 SP - e51601 C1 - eLife 2019;8:e51601 DO - 10.7554/eLife.51601 UR - https://doi.org/10.7554/eLife.51601 AB - 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. KW - mitochondria KW - metabolism KW - membrane fusion KW - spermatogenesis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -