title: Mitochondrial fission factor Drp1 maintains oocyte quality via dynamic rearrangement of multiple organelles.
abstract: Mitochondria are dynamic organelles that change their morphology by active fusion and fission in response to cellular signaling and differentiation. 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, as well as analyzing a human patient harboring a point mutation in Drp1, 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, and their organelle aggregation is related to germ cell formation and epigenetic regulation. 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 age-dependent manner. Mitochondria were highly aggregated with other organelles, such as the ER and secretory vesicles, in KO oocyte, which resulted in impaired Ca(2+) 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.
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan; National Institute for Environmental Studies, Center for Environmental Risk Research, Tsukuba 305-8506, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Udagawa
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Ishihara
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan; Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Laboratory Animal Sciences Section, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsukamoto
authors.affiliation: National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kawano
authors.affiliation: National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyado
authors.affiliation: Laboratory for Transgenic Technology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shitara
authors.affiliation: Pharmaceutical Sciences, Nagasaki International University, Sasebo 859-3298, Japan.
authors.forename: Sadaki
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Medicine and Bioregulatory Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Mihara
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan; Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. Electronic address: ishihara_naotada@kurume-u.ac.jp.
authors.forename: Naotada
authors.initials: N
authors.lastname: Ishihara
mesh_terms: D000375:Aging; D000818:Animals; D002118:Calcium; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005298:Fertility; D005786:Gene Expression Regulation / Q000502:physiology*; D006107:Granulosa Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D006080:Ovarian Follicle / Q000502:physiology*; D010060:Ovulation / Q000502:physiology*
chemical_list: C486391:Dnm1l protein, mouse; D034281:Dynamins; D002118:Calcium