Redistribution of fragmented mitochondria ensures symmetric organelle partitioning and faithful chromosome segregation in mitotic mouse zygotes

• Published in: eLife Vol. 13
• Main Authors: Gekko, Haruna, Nomura, Ruri, Kuzuhara, Daiki, Kaneyasu, Masato, Koseki, Genpei, Adhikari, Deepak, Mio, Yasuyuki, Carroll, John, Kono, Tomohiro, Funahashi, Hiroaki, Wakai, Takuya
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 11.08.2025; eLife Sciences Publications, Ltd
• Subjects: Animals; binuclear formation; Blastomeres; Calcium (reticular); Calcium - metabolism; Cell cycle; Cell division; Chromosome Segregation; Chromosomes; Cytoplasm; Daughters; Developmental Biology; Dynamin; Dynamin-related protein 1; Dynamins - genetics; Dynamins - metabolism; Embryos; Endoplasmic reticulum; Extrachromosomal inheritance; Female; Mice; Microscopy; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Mitochondrial Dynamics; Mitochondrial inheritance; Mitosis; organelle inheritance; Organelles; preimplantation development; Zygote - metabolism; Zygote - physiology; Zygotes; mouse; binuclear formation; chromosome segregation; Dynamin-related protein 1; developmental biology; organelle inheritance; preimplantation development; mitochondrial dynamics
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.99936

In cleavage-stage embryos, preexisting organelles partition evenly into daughter blastomeres without significant cell growth after symmetric cell division. The presence of mitochondrial DNA within mitochondria and its restricted replication during preimplantation development makes their inheritance particularly important. While chromosomes are precisely segregated by the mitotic spindle, the mechanisms controlling mitochondrial partitioning remain poorly understood. In this study, we investigate the mechanism by which Dynamin-related protein 1 (Drp1) controls the mitochondrial redistribution and partitioning during embryonic cleavage. Depletion of Drp1 in mouse zygotes causes marked mitochondrial aggregation, and the majority of embryos arrest at the 2 cell stage. Clumped mitochondria are located in the center of mitotic Drp1-depleted zygotes with less uniform distribution, thereby preventing their symmetric partitioning. Asymmetric mitochondrial inheritance is accompanied by functionally inequivalent blastomeres with biased ATP and endoplasmic reticulum Ca 2+ levels. We also find that marked mitochondrial centration in Drp1-depleted zygotes prevents the assembly of parental chromosomes, resulting in chromosome segregation defects and binucleation. Thus, mitochondrial fragmentation mediated by Drp1 ensures proper organelle positioning and partitioning into functional daughters during the first embryonic cleavage.