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Osamu Kuge Last modified date:2018.06.21

Professor / Organic and Biological Chemistry
Department of Chemistry
Faculty of Sciences


Graduate School
Undergraduate School
Other Organization


E-Mail
Academic Degree
Dr. of Pharmaceutical Sciences
Country of degree conferring institution (Overseas)
No
Field of Specialization
Biochemistry, Cell Biology, Genetics
Total Priod of education and research career in the foreign country
00years00months
Research
Research Interests
  • Biosynthetic regulation and intracellular transport of phospholipids
    keyword : Biological Membranes, Phospholipids, Biosynthetic Regulation, Intracellular Transport
    2000.01.
Academic Activities
Reports
1. Kuge O, Nishijima M., Biosynthetic regulation and intracellular transport of phosphatidylserine in mammalian cells, J Biochem., 133(4):397-403, 2003.04.
2. Kuge O, Nishijima M., Phosphatidylserine synthase I and II of mammalian cells., Biochim Biophys Acta., 1348(1-2):151-6., 1997.09.
3. Nishjima M, Kuge O, Hanada K., Mammalian cell mutants of membrane phospholipid biogenesis., Trends Cell Biol., 7(8):324-9., 1997.08.
Papers
1. Non Miyata, Naoto Goda, Keiji Matsuo, Takeshi Hoketsu, Osamu Kuge, Cooperative function of Fmp30, Mdm31, and Mdm32 in Ups1-independent cardiolipin accumulation in the yeast Saccharomyces cerevisiae, Scientific Reports, 10.1038/s41598-017-16661-2, 7, 1, 2017.12, Cardiolipin (CL) is synthesized from phosphatidic acid (PA) through a series of enzymatic reactions occurring at the mitochondrial inner membrane (MIM). Ups1-Mdm35 mediates PA transfer from the mitochondrial outer membrane (MOM) to the MIM in the yeast Saccharomyces cerevisiae. Deletion of UPS1 leads to a ~80% decrease in the cellular CL level. However, the CL accumulation in ups1∆ cells is enhanced by the depletion of Ups2, which forms a protein complex with Mdm31 and mediates phosphatidylserine (PS) transfer from the MOM to the MIM for phosphatidylethanolamine (PE) synthesis by a PS decarboxylase, Psd1. In this study, we found that the accumulation of CL in ups1∆ cells was enhanced by deletion of not only UPS2, but also PSD1 and CHO1 encoding a PS synthase, suggesting that low PE levels in mitochondria were relevant to the enhancement of CL accumulation in ups1∆ cells. Furthermore, the Ups1-independent and low-level PE-enhanced CL accumulation was shown to depend on the functions of FMP30, MDM31, and MDM32. In addition, the physical interactions of Fmp30 with Mdm31 and Mdm32 were revealed. Thus, when the mitochondrial PE level is reduced, Fmp30, Mdm31, and Mdm32 seem to function cooperatively for the accumulation of CL in a UPS1-independent manner..
2. Non Miyata, Yasunori Watanabe, Yasushi Tamura, Toshiya Endo, Osamu Kuge, Phosphatidylserine transport by Ups2-Mdm35 in respiration-active mitochondria, Journal of Cell Biology, 10.1083/jcb.201601082, 214, 1, 77-88, 2016.07, Phosphatidylethanolamine (PE) is an essential phospholipid for mitochondrial functions and is synthesized mainly by phosphatidylserine (PS) decarboxylase at the mitochondrial inner membrane. In Saccharomyces cerevisiae, PS is synthesized in the endoplasmic reticulum (ER), such that mitochondrial PE synthesis requires PS transport from the ER to the mitochondrial inner membrane. Here, we provide evidence that Ups2-Mdm35, a protein complex localized at the mitochondrial intermembrane space, mediates PS transport for PE synthesis in respiration-active mitochondria. UPS2- and MDM35-null mutations greatly attenuated conversion of PS to PE in yeast cells growing logarithmically under nonfermentable conditions, but not fermentable conditions. A recombinant Ups2-Mdm35 fusion protein exhibited phospholipidtransfer activity between liposomes in vitro. Furthermore, UPS2 expression was elevated under nonfermentable conditions and at the diauxic shift, the metabolic transition from glycolysis to oxidative phosphorylation. These results demonstrate that Ups2-Mdm35 functions as a PS transfer protein and enhances mitochondrial PE synthesis in response to the cellular metabolic state..
3. Miyata N, Miyoshi T, Yamaguchi T, Nakazono T, Tani M, Kuge O, VID22 is required for transcriptional activation of the PSD2 gene in the yeast Saccharomyces cerevisiae, BIOCHEMICAL JOURNAL, 10.1042/BJ20150884, 472, 319-328, 2015.12.
4. Reiko Ban-Ishihara, Shiho Tomohiro-Takayama, Motohiro Tani, Jacques Baudier, Naotada Ishihara, Osamu Kuge, COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1, FEBS LETTERS, 10.1016/j.febslet.2015.08.039, 589, 20, 3126-3132, 2015.10.
5. Kuroda T, Tani M, Moriguchi A, Tokunaga S, Higuchi T, Kitada S, Kuge O., FMP30 is required for the maintenance of a normal cardiolipin level and mitochondrial morphology in the absence of mitochondrial phosphatidylethanolamine synthesis., Mol Microbiol., 10.1111/j.1365-2958.2011.07569.x, 80, 1, 248-265, 2011.04.
6. Tani M, Kuge O., Requirement of a specific group of sphingolipid-metabolizing enzyme for growth of yeast Saccharomyces cerevisiae under impaired metabolism of glycerophospholipids., Mol Microbiol. , 78, 2, 395-413, 2010.09.
7. Gilquin, B., Taillebourg, E., Cherradi, N., Hubstenberger, A., Gay, O., Merle, N., Assard, N., Fauvarque, M.-O., Tomohiro, S., Kuge, O., and Baudier, J., The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes., Mol Cell Biol., 10.1128/MCB.00007-10, 30, 8, 1984-1996, 2010.04.
8. Shiho Tomohiro, Ayako Kawaguti, Yukiyo Kawabe, Sakae Kitada, Osamu Kuge, Purification and characterization of human phosphatidylserine synthases 1 and 2, Biochem. J., 2009.03.
9. Tomoko Ohsawa, Masahiro Nishijimam and Osamu Kuge, Functional analysis of Cinese hamster phosphatidylserine synthase 1 trough systematic alanine mutagenesis, Biochem. J., 10.1042/BJ20040443, 381, 853-859, Vol. 381, pp853-859, 2004.01.
10. Osamu Kuge, Kazuhide Hasegawa, Tomoko Ohsawa, Kyoko Saito, and Masahiro Nishijima, Purification and characterization of Chinese hamster phosphatidylserine synthase 2, J. Biol. Chem., 10.1074/jbc.M307270200, 278, 43, 42692-42698, Vol. 278, No. 43, pp. 42692-42698, 2003.10.
11. Osamu Kuge, Yoshio Yamakawa, and Masahiro Nishijima, Enhancement of transport-dependent decarboxylation of phosphatidylserine by S100B protein in permeabilized Chinese hamster ovary cells, J.Biol. Chem., Vol. 276, No. 26, pp.23700-23706, 2001.06.
12. Kazuo Emoto, Osamu Kuge, Masahiro Nishijima, and Masato Umeda, Isolation of a Chinese hamster ovary cell mutant defective in intramitochondrial transport of phosphatidylserine, Proc.Natl. Acad. Sci. USA, Vol. 96, No. 22, pp.12400-12405, 1999.10.
13. Osamu Kuge, Kyoko Saito, and Nishijima Masahiro, Control of phosphatidylserine synthase II activity in Chinese hamster ovary cells, J. Biol. Chem., Vol. 274, No.34, pp.23844-23849, 1999.08.
14. Kyoko Saito, Masahiro Nishijima, and Osamu Kuge, Genetic evidence that phosphatidylserine synthase II catalyzes the conversion of phosphatidylethanolamine to phosphatidylserine in Chinese hamster ovary cells, J. Biol. Chem., Vol. 273. No. 27, pp. 17199-17205, 1998.06.
15. Osamu Kuge, Kazuhide Hasegawa, Kyoko Saito, and Masahiro Nishijima, Control of phosphatidylserine biosynthesis through phosphatidylserine-mediated inhibition of phosphatidylserine synthase I in Chinese hamster ovary cells, Proc. Natl. Acad. Sci. USA, Vol. 95, pp.4199-4203, 1998.04.
16. Osamu Kuge, Kyoko Saito, and Masahiro Nishijima, Cloning of a Chinese hamster ovary (CHO) cDNA encoding phosphatidylserine synthase (PSS) II, overexpression of which suppresses the phosphatidylserine biosynthetic defect of a PSS I-lacking mutant of CHO-K1 cells, J. Biol. Chem., Vol. 272, No.31, pp. 19133-19139, 1997.08.
17. Kuge O, Saito K, Kojima M, Akamatsu Y, Nishijima M., Post-translational processing of the phosphatidylserine decarboxylase gene product in Chinese hamster ovary cells., Biochem J. , 319 (Pt 1):33-8, 1996.10.
18. Aoki K, Suzuki K, Sugano T, Tasaka T, Nakahara K, Kuge O, Omori A, Kasai M., A novel gene, Translin, encodes a recombination hotspot binding protein associated with chromosomal translocations., Nat Genet., 10(2):167-74, 1995.06.
19. Osamu Kuge, Christiane Dascher, Lelio Orci, Tony Rowe, Mylene Amherdt, Helen Plutner, Mariella Ravazzola, Gary Tanigawa, James E. Rothman, and William E. Balch, Sar1 promotes vesicle budding from the endoplasmic reticulum but not Golgi compartments, J. Cell Biol., Vol. 125, No. 1, pp. 51-65, 1994.04.
20. Osamu Kuge, Sayuri Hara-Kuge, Lelio Orci, Mariella Ravazzola, Mylene Amherdt, Gary Tanigawa, Felix T. Wieland, and James E. Rothman, zeta-COP, a subunit of coatomer is required for COP-coated vesicle assembly, J. Cell Biol., Vol. 123, No. 6, pp. 1727-1734, 1993.12.
21. Osamu Kuge, Masahiro Nishijima, and Yuzuru Akamatsu, A Chinese hamster cDNA encoding a protein essential for phosphatidylserine synthase I activity, J. Biol. Chem., Vol. 266, No. 35, pp. 24184-24189, 1991.12.
22. Osamu Kuge, Masahiro Nishijima, and Yuzuru Akamatsu, A cloned gene encoding phosphatidylserine decarboxylase complements the phosphatidylserine biosynthetic defect of a Chinese hamster ovary cell mutant, J. Biol. Chem., Vol. 266, No. 10, pp. 6370-6376, 1991.01.
23. Osamu Kuge, Masahiro Nishijima, and Yuzuru Akamatsu, Isolation of a somatic cell mutant defective in phosphatidylserine biosynthesis, Proc. Natl. Acad. Sci. USA, Vol. 82, pp. 1926-1930, 1985.04.
24. Kuge O, Nishijima M, Akamatsu Y., Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. III. Genetic evidence for utilization of phosphatidylcholine and phosphatidylethanolamine as precursors., J Biol Chem., 261(13):5795-8, 1986.02.
25. Osamu Kuge, Masahiro Nishijima, and Yuzuru Akamatsu, Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells: II. Isolation and characterization of phosphatidylserine auxotrophs, J. Biol. Chem., Vol. 261, No. 13, pp. 5790-5794, 1986.05.
Presentations
1. Osamu Kuge, Non Miyata, Intramitochondrial transport of phosphatidylserine by Ups2-Mdm35, 第89回日本生化学会大会 合同大会, 2016.09.
2. Osamu Kuge, Mitochondrial lipid transport and biosynthesis: a role of Ups2-Mdm35, FEBS Advanced Course: Lipid-protein interactions and organelle function, 2016.09.