Mitochondrial fission factor Drp1 maintains oocyte quality via dynamic rearrangement of multiple organelles

Osamu Udagawa, Takaya Ishihara, Maki Maeda, Yui Matsunaga, Satoshi Tsukamoto, Natsuko Kawano, Kenji Miyado, Hiroshi Shitara, Sadaki Yokota, Masatoshi Nomura, Katsuyoshi Mihara, Noboru Mizushima, Naotada Ishihara

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37 Citations (Scopus)

Abstract

Mitochondria are dynamic organelles that change their morphology by active fusion and fission in response to cellular signaling and differentiation [1, 2]. 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 [8-10]. However, the underlying molecular mechanisms of organelle dynamics during the development and aging of oocytes have not been well understood. Here, we analyzed oocyte-specific mitochondrial fission factor Drp1-deficient mice and found that mitochondrial fission is essential for follicular maturation and ovulation in an agedependent manner. Mitochondria were highly aggregated with other organelles, such as the ER and secretory vesicles, in KO oocyte, which resulted in impaired Ca2+ signaling, intercellular communication via secretion, and meiotic resumption. We further found that oocytes from aged mice displayed reduced Drp1-dependent mitochondrial fission and defective organelle morphogenesis, similar to Drp1 KO oocytes. On the basis of these findings, it appears that mitochondrial fission maintains the competency of oocytes via multiorganelle rearrangement.

Original languageEnglish
Pages (from-to)2451-2458
Number of pages8
JournalCurrent Biology
Volume24
Issue number20
DOIs
Publication statusPublished - Oct 20 2014

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Udagawa, O., Ishihara, T., Maeda, M., Matsunaga, Y., Tsukamoto, S., Kawano, N., ... Ishihara, N. (2014). Mitochondrial fission factor Drp1 maintains oocyte quality via dynamic rearrangement of multiple organelles. Current Biology, 24(20), 2451-2458. https://doi.org/10.1016/j.cub.2014.08.060