Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD 21218, United States of America.
Biochim Biophys Acta Gen Subj. 2021 May;1865(5):129845. doi: 10.1016/j.bbagen.2021.129845. Epub 2021 Jan 19.
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.
We used genetic ablation of Mff (mitochondrial fission factor) in mice to investigate the role of mitochondrial fission during mammalian spermatogenesis.
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.
Mff is required for organization of the mitochondrial sheath in mouse sperm.
Mitochondrial fission plays an important role in regulating mitochondrial organization during a complex developmental process.
线粒体裂变可与融合作用相互平衡，从而维持细胞器的形态，但它在发育过程中的作用仍未得到充分描述。哺乳动物精子发生是一个复杂的发育过程，涉及到线粒体形状和组织的几次剧烈变化。在精原细胞中，线粒体通常较小且呈球形，在减数分裂过程中拉长，在单倍体圆形精子中碎片化。在精子成熟的末期，小的线粒体球体排列在轴丝上，伸长并紧密缠绕中段以形成线粒体鞘，这对于为鞭毛运动提供燃料至关重要。目前尚不清楚这些线粒体形态变化是如何被调节的，以及它们如何影响精子的发育。
我们使用小鼠中 Mff（线粒体裂变因子）的基因缺失来研究线粒体裂变在哺乳动物精子发生中的作用。
我们的分析表明，Mff 是单倍体圆形精子中线粒体碎片化和延长精子中段中线粒体排列所必需的。在 Mff 突变小鼠中，圆形精子具有异常伸长的线粒体，这些线粒体经常出现中央收缩，提示发生了失败的裂变事件。在延长的精子和精子中，线粒体鞘是不连贯的，含有肿胀的线粒体，细胞器之间有很大的间隙。Mff 突变精子中的这些线粒体异常与呼吸链复合物 IV 活性降低、精子形态和运动异常以及生育能力降低有关。
Mff 是小鼠精子中线粒体鞘组织所必需的。
线粒体裂变在调节复杂发育过程中线粒体的组织中起着重要作用。
