ミトコンドリアの進化の多様性

2015 Fiscal Year Annual Research Report

• Project Area: "Matryoshka"-type evolution of eukaryotes
• Project/Area Number: 23117005
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: 野崎 智義 国立感染症研究所, その他部局等, その他 (60198588)
• Co-Investigator(Kenkyū-buntansha): 石川 香 筑波大学, 生命環境科学研究科(系), 助教 (40734827) ; 橋本 哲男 筑波大学, 生命環境科学研究科(系), 教授 (50208451) ; 黒田 誠 国立感染症研究所, その他部局等, その他 (80317411)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: オルガネラ / 内部共生 / 進化 / 寄生 / ミトコンドリア

Outline of Annual Research Achievements

赤痢アメーバの嫌気的ミトコンドリアMRO（マイトソーム）の新規膜タンパク質を4種類同定し、その局在・物性・生理機能等を解明した。マイトソームのPAPS輸送体を同定し、生理機能を証明した。マイトソームの分裂において2種類のDRPが赤痢アメーバの分裂に関与することを明らかにした。
3種の嫌気性原生生物フォルニカータの比較トランスクリプトーム、ゲノム解析から、MROの嫌気的エネルギー産生経路の進化において、関連酵素の獲得や別の酵素への転換に遺伝子水平転移が大きく貢献していることを明らかとした。非モデル真核微生物のミトコンドリアゲノム解析を進め、クリプティスタ生物群の原始系統、クロララクニオン藻などに関するデータからミトコンドリアゲノムの多様性に関する新知見を得た。
環形動物と魚類を交互寄生する粘液胞子虫のゲノムの極度に縮退したゲノムを解析した。胞子ステージから栄養体ステージへの推移に関与する遺伝子を動物腸管内のトランスクリプトーム解析にて特定し、ゲノム縮退と従属的な生活環の関連性を解明した。
ミトコンドリア(mt)DNA変異病原性理解のため、mtDNAに病原性突然変異を有し、かつ核DNAにコードされたミトコンドリア分裂因子Drp1を組織特異的に欠損したマウスを用い、病態がより重篤化する傾向を認めた。核コード遺伝子がmtDNAの病原性突然変異による病態発症の抑制に密接に関わっており、核‐ミトコンドリア間クロストークが生体の機能に影響を与えていることを示した。mtDNA tRNA Lys遺伝子点突然変異保有マウスにおいて加齢によって軽度の筋委縮や腎不全等の発症を発見した。独立してヒトミトコンドリア病患者と相同部位に突然変異を有するマウス培養細胞株を見出し、当該変異の濃縮に成功した。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Dalhousie University(Canada)
  • Country Name: Canada
  • Counterpart Institution: Dalhousie University
• [Journal Article] Screening and discovery of lineage-specific mitosomal membrane proteins in Entamoeba histolytica. (2016)
  • Author(s): Santos, H. J., Imai, K., Hanadate, Y., Fukasawa, Y., Oda, T., Mi-ichi, F., and Nozaki, T.
  • Journal Title: Mol. Biochem. Parasitol Volume: ? Pages: ?
  • DOI: 10.1016/j.molbiopara.2016.01.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Entamoeba thiol-based redox metabolism: a potential target for drug development. (2016)
  • Author(s): Jeelani, G. and Nozaki, T.
  • Journal Title: Mol. Biochem. Parasitol. Volume: ? Pages: ?
  • DOI: 10.1016/j.molbiopara.2016.01.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of acetyl-CoA synthetase (ADP-forming) and acetate kinase (PPi-forming) in ATP and PPi supply in Entamoeba histolytica. (2016)
  • Author(s): Pineda, E., Vázquez, C., Encalada, R., Nozaki, T., Sato, E., Hanadate, Y., Néquiz, M, Olivos-García, A., Moreno-Sánchez, R., Saavedra, E.
  • Journal Title: Biochim. Biophys. Acta Volume: 1860 Pages: 1163-1172
  • DOI: 10.1016/j.bbagen.2016.02.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Endoplasmic reticulum-resident Rab8A GTPase is involved in phagocytosis in the protozoan parasite Entamoeba histolytica. (2016)
  • Author(s): Hanadate, Y., Saito-Nakano, Y., Nakada-Tsukui, K., and Nozaki, T.
  • Journal Title: Cell Microbiol Volume: ? Pages: ?
  • DOI: 10.1111/cmi.12570
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative genomics of mitochondria in chlorarachniophyte algae: endosymbiotic gene transfer and organellar genome dynamics. (2016)
  • Author(s): Tanifuji G, Archibald JM, Hashimoto T.
  • Journal Title: Sci Rep Volume: 6 Pages: 21016
  • DOI: 10.1038/srep21016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phenotypic and transcriptional profiling in Entamoeba histolytica reveal costs to fitness and adaptive responses associated with metronidazole resistance. (2015)
  • Author(s): Penuliar, G. M., Nakada-Tsukui, K., and Nozaki, T.
  • Journal Title: Front Microbiol Volume: 6 Pages: 354
  • DOI: 10.3389/fmicb.2015.00354
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Atg8 is involved in endosomal and phagosomal acidification in the parasitic protist Entamoeba histolytica. (2015)
  • Author(s): Picazarri, K., Nakada-Tsukui, K., Tsuboi, K., Miyamoto, E., Watanabe, N., Kawakami, E., and Nozaki, T.
  • Journal Title: Cell Microbiol Volume: 17 Pages: 1510-1522
  • DOI: 10.1111/cmi.12453
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The mitochondrial genomes of a myxozoan genus Kudoa are extremely divergent in Metazoa. (2015)
  • Author(s): Takeuchi, F., Sekizuka, T., Ogasawara, Y., Yokoyama, H., Kamikawa, R., Inagaki, Y., Nozaki, T., Sugita-Konishi, T., Ohnishi, T, and Kuroda, M.
  • Journal Title: PLoS ONE Volume: 10 Pages: e0132030
  • DOI: 10.1371/journal.pone.0132030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of nucleotide sequence typing for Kudoa septempunctata, a flounder parasite causing foodborne disease. (2015)
  • Author(s): Takeuchi, F., Ogasawara, Y., Kato, K., Sekizuka, T., Nozaki, T., Sugita-Konishi, Y., Ohnishi, T., and Kuroda, M.
  • Journal Title: J Fish Dis Volume: 39 Pages: 667-72
  • DOI: doi:10.1111/jfd.12395. 2015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of natural inhibitors of Entamoeba histolytica cysteine synthase from microbial secondary metabolites. (2015)
  • Author(s): Mori, M., Jeelani, G., Masuda, Y., Sakai, K., Nakada-Tsukui, K., Waluyo, D., Tarwadi, Watanabe, Y., Nonaka, K., Matsumoto, A., Omura, S., Nozaki, T., and Shiomi, K.
  • Journal Title: Front Microbiol Volume: 6 Pages: 962
  • DOI: 10.3389/fmicb.2015.00962
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Discovery of PPi-type phosphoenolpyruvate carboxykinase genes in eukaryotes and bacteria. (2015)
  • Author(s): Chiba, Y., Kamikawa, R., Nakada-Tsukui, K, Saito-Nakano, Y., and Nozaki, T.
  • Journal Title: J Biol Chem Volume: 290 Pages: 23960-23970
  • DOI: 10.1074/jbc.M115.672907
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evidence that Entamoeba histolytica mitochondrial carrier family links mitosomal and cytosolic pathways through exchange of PAPS and ATP. (2015)
  • Author(s): Mi-ichi, F., Nozawa, A., Yoshida, H., Tozawa, Y., Nozaki, T.
  • Journal Title: Eukaryot Cell Volume: 14 Pages: 1144-1150
  • DOI: 10.1128/EC.00130-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Metabolic Capacity of Mitochondrion-related Organelles in the Free-living Anaerobic Stramenopile Cantina marsupialis. (2015)
  • Author(s): Noguchi F, Shimamura S, Nakayama T, Yazaki E, Yabuki A, Hashimoto T, Inagaki Y, Fujikura K, Takishita K.
  • Journal Title: Protist Volume: 166 Pages: 534-550
  • DOI: 10.1016/j.protis.2015.08.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phylogeny and evolution of apicoplasts and apicomplexan parasites. (2015)
  • Author(s): Arisue N, Hashimoto T.
  • Journal Title: Parasitol Int Volume: 64 Pages: 254-259
  • DOI: 10.1016/j.parint.2014.10.005
  • Peer Reviewed
• [Journal Article] G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice. (2015)
  • Author(s): Shimizu A, Mito T, Hashizume O, Yonekawa H, Ishikawa K, Nakada K, Hayashi J.
  • Journal Title: Biochem Biophys Res Commun. Volume: 459 Pages: 66-70
  • DOI: 10.1016/j.bbrc.2015.02.070
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mouse somatic mutation orthologous to MELAS A3302G mutation in the mitochondrial tRNA(Leu(UUR)) gene confers respiration defects. (2015)
  • Author(s): Shimizu A, Enoki S, Ishikawa K, Mito T, Obata K, Nagashima R, Yonekawa H, Nakada K, Hayashi J.
  • Journal Title: Biochem Biophys Res Commun. Volume: 467 Pages: 1097-102
  • DOI: 10.1016/j.bbrc.2015.09.072
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects. (2015)
  • Author(s): Hashizume O, Ohnishi S, Mito T, Shimizu A, Ishikawa K, Nakada K, Soda M, Mano H, Togayachi S, Miyoshi H, Okita K, Hayashi J.
  • Journal Title: Sci Rep Volume: 5 Pages: 10434
  • DOI: 10.1038/srep10434
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Metabolism, pathogenesis, and unique organelles in the enteric protozoon Entamoeba histolytica. (2015)
  • Author(s): Nozaki, T.
  • Organizer: The 44th Annual Convention and Scientific Meeting of the Philippine Society for Microbiology.
  • Place of Presentation: Pasay City, The Philippines.
  • Year and Date: 2015-07-16
  • Int'l Joint Research / Invited