Although mitochondrial morphology is well-known for its role in cellular homeostasis, there is surprisingly little knowledge on whether mitochondrial remodeling is required for postnatal germ cell development. In this study, we investigated the functions of MFN1 and MFN2, two GTPases in mitochondrial fusion, during early spermatogenesis. We observed increased MFN expressions along with increased mitochondrial and endoplasmic reticulum (ER) activities during spermatogonial differentiation. Deletion of either Mfn led to DNA oxidation and apoptosis specifically in differentiating spermatogonia and spermatocytes, which in turn caused male infertility. We further found MFN2 regulated spermatogenesis by modulating both mitochondrial and ER functions, a mechanism distinct from that of MFN1. Defects of germ cell development in MFN2 mutants were corrected by MFN2 at either mitochondria or ER but not by MFN1. Our study thus reveals an essential requirement of MFN-mediated mitochondrial and ER coordination in spermatogenesis, providing critical insights into mitochondrial determinants of male fertility.

尽管线粒体形态因其在细胞稳态中的作用而众所周知，但令人惊讶的是，对于产后生殖细胞发育是否需要线粒体重塑的知识很少。在这项研究中，我们调查了早期精子发生过程中MGT1和MFN2这两个GTPases在线粒体融合中的功能。我们观察到在精原细胞分化过程中MFN表达增加，线粒体和内质网（ER）活性也增加。删除任一Mfn导致DNA氧化和凋亡，特别是在分化精原细胞和精母细胞时，进而引起男性不育。我们还发现，MFN2通过调节线粒体和ER功能来调节精子发生，这一机制不同于MFN1。MFN2突变体中生殖细胞发育的缺陷可通过线粒体或ER处的MFN2进行校正，但不能通过MFN1进行。因此，我们的研究揭示了MFN介导的线粒体和ER协调在精子发生中的基本要求，从而为雄性育性的线粒体决定因素提供了重要的见识。