| Project/Area Number |
15K08449
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Research Collaborator |
SHIRAI SERINA
KOJIMA YUKI
MATSUDA RISA
YOKOTA NATSUKI
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | マラリア原虫 / TCA回路 / プリンヌクレオチド生合成 / リンゴ酸：キノン酸化還元酵素 / フマラーゼ / オキサロ酢酸 / 代謝ネットワーク / 抗マラリア薬 / 比較ゲノム解析 / 比較プロテオーム解析 / 病態重症化 / 妊娠 / 代謝活性 / MQO / エネルギー代謝 / フマル酸 / リンゴ酸 / 赤血球ステージ |
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| Outline of Final Research Achievements |
In Plasmodium parasites, TCA cycle is not essential for survival of asexual-blood-stage parasites, but is required for survival of mosquito-stage parasites. Whereas, two of the eight mitochondrial TCA cycle enzymes, fumarate hydratase (FH) and malate:quinone oxidoreductase (MQO), could not be genetically ablated in asexual-blood-stage Plasmodium falciparum. However, the importance of FH and MQO for asexual-stage parasite viability and growth in cerebral malaria is unclear. In this study, we revealed that MQO is a key molecule for metabolic cross-talk between purine salvage pathway and TCA cycle in rodent malaria parasites, Plasmodium berghei ANKA, and is involved in parasite viability during the blood stage. The finding that MQO is involved in the viability, the growth of asexual-blood-stage parasites and the development of experimental cerebral malaria suggest that MQO would be a potential target for the treatment of severe malaria.
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