Biased inheritance of mitochondria during asymmetric cell division in the mouse oocyte

Abstract

SummaryA fundamental rule of cell division is that daughter cells inherit half the DNA complement and an appropriate proportion of cellular organelles. The highly asymmetric cell divisions of female meiosis present a different challenge because one of the daughters, the polar body, is destined to degenerate, putting at risk essential maternally inherited organelles such as mitochondria. We have therefore investigated mitochondrial inheritance during the meiotic divisions of the mouse oocyte. We find that mitochondria are aggregated around the spindle by a dynein-mediated mechanism during meiosis I, and migrate together with the spindle towards the oocyte cortex. However, at cell division they are not equally segregated and move instead towards the oocyte-directed spindle pole and are excluded from the polar body. We show that this asymmetrical inheritance in favour of the oocyte is not caused by bias in the spindle itself but is dependent on an intact actin cytoskeleton, spindle-cortex proximity, and cell cycle progression. Thus, oocyte-biased inheritance of mitochondria is a variation on rules that normally govern organelle segregation at cell division, and ensures that essential maternally inherited mitochondria are retained to provide ATP for early mammalian development.

Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases

“…The spindle-chromosome complex was surrounded by amounts of mitochondria in some oocytes ( Figure 2A). Corroborating recent findings, mitochondria aggregated around the spindle during oocyte maturation and were then distributed universally throughout the MII oocyte (Dalton and Carroll, 2013). We explain this behavior through the notion that the spindle-chromosome complex requires ATP to reassemble, migrate, and divide during meiosis, which resulted in the surrounding mitochondria aggregation.…”

“…Then offspring were delivered from foster mothers. See also Table S1. organelles, such as mitochondria, and are composed almost entirely of chromatids (Dalton and Carroll, 2013;Pikó and Taylor, 1987). Thus, a minimal carryover of donor (patient) mtDNA genotype is expected in the reconstituted embryos and offspring produced by PB transfer.…”

Mitochondrial Fission Factor Drp1 Maintains Oocyte Quality via Dynamic Rearrangement of Multiple Organelles

“…The in vivo role of mitochondrial fission in mammals has been examined by using tissue-specific knockout (KO) mice of the mitochondria fission-regulating GTPase Drp1 [3,4], as well as analyzing a human patient harboring a point mutation in Drp1 [5], showing that Drp1 is essential for embryonic and neonatal development and neuronal function. During oocyte maturation and aging, structures of various membrane organelles including mitochondria and the endoplasmic reticulum (ER) are changed dynamically [6,7], and their organelle aggregation is related to germ cell formation and epigenetic regulation [8][9][10]. However, the underlying molecular mechanisms of organelle dynamics during the development and aging of oocytes have not been well understood.…”

Keep the fire burning: Current avenues in the quest of treating mitochondrial disorders

“…Polar bodies contain only a few mitochondria (Dalton and Carroll, 2013) but share the same genetic material and developmental potential as pronuclei or spindle complexes inside the ooplasm (Hino et al, 2013;Wakayama and Yanagimachi, 1998). Comparing PNT and ST with polar body genome transfer in mice, lower levels of donor mtDNA carry-over were observed using the new technique (Wang et al, 2014).…”