Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yuichi Matsushima Last modified date:2018.01.11

Assistant Professor / Department of Clinical Chemistry and Laboratory Medicine / Department of Basic Medicine / Faculty of Medical Sciences

1. Takashi Matsumoto, Takeshi Uchiumi, Keisuke Monji, Mikako Yagi, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, masaki shiota, Masatoshi Eto, Dongchon Kang, Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties
Importance of stem cell plasticity, Oncogenesis, 10.1038/s41389-017-0009-3, 6, 11, 2017.11, Tumor heterogeneity can be traced back to a small subset of cancer stem cells (CSCs), which can be derived from a single stem cell and show chemoresistance. Recent studies showed that CSCs are sensitive to mitochondrial targeting antibiotics such as doxycycline. However, little is known about how cancer cells undergo sphere formation and how antibiotics inhibit CSC proliferation. Here we show that under sphere-forming assay conditions, prostate cancer cells acquired CSC-like properties: promoted mitochondrial respiratory chain activity, expression of characteristic CSC markers and resistance to anticancer agents. Furthermore, those CSC-like properties could reversibly change depending on the culture conditions, suggesting some kinds of CSCs have plasticity in tumor microenvironments. The sphere-forming cells (i.e. cancer stem-like cells) showed increased contact between mitochondria and mitochondrial associated-endoplasmic reticulum (ER) membranes (MAM). Mitochondrial targeting doxycycline induced activating transcription factor 4 (ATF4) mediated expression of ER stress response and led to p53-upregulated modulator of apoptosis (PUMA)-dependent apoptosis only in the cancer stem-like cells. We also found that doxycycline effectively suppressed the sphere formation in vitro and blocked CD44v9-expressing tumor growth in vivo. In summary, these data provide new molecular findings that monolayer cancer cells acquire CSC-like properties in a reversible manner. These findings provide important insights into CSC biology and a potential new treatment of targeting mitochondria dependency..
2. Mikako Yagi, Takeshi Uchiumi, Noriaki Sagata, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, Dongchon Kang, Neural-specific deletion of mitochondrial p32/C1qbp leads to leukoencephalopathy due to undifferentiated oligodendrocyte and axon degeneration, Scientific Reports, 10.1038/s41598-017-15414-5, 7, 1, 2017.12, Mitochondrial dysfunction is a critical step in the pathogenesis of many neurodegenerative diseases. The p32/ C1qbp gene functions as an essential RNA and protein chaperone in mitochondrial translation, and is indispensable for embryonic development. However, little is known about the consequences of mitochondrial dysfunction of p32 deletion in the brain development. Here, we found that mice lacking p32 in the central nervous system (p32cKO mice) showed white matter degeneration accompanied by progressive oligodendrocyte loss, axon degeneration and vacuolation in the mid brain and brain stem regions. Furthermore, p32cKO mice died within 8 weeks of birth. We also found that p32-deficient oligodendrocytes and neurons showed reduced oligodendrocyte differentiation and axon degeneration in primary culture. We show that mitochondrial disruption activates an adaptive program known as the integrated stress response (ISR). Mitochondrial respiratory chain function in oligodendrocytes and neurons is, therefore, essential for myelination and axon maintenance, respectively, suggesting that mitochondrial respiratory chain dysfunction in the central nervous system contributes to leukoencephalopathy..
3. Toshiro Saito, Takeshi Uchiumi, Mikako Yagi, Rie Amamoto, Daiki Setoyama, Yuichi Matsushima*, Dongchon Kang, Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and activates stress responses, CARDIOVASCULAR RESEARCH, 10.1093/cvr/cvx095, 113, 10, 1173-1185, 2017.08.
4. Yuichi Matsushima*, Yuta Hirofuji, Masamune Aihara, Yue Song, Takeshi Uchiumi, Laurie S Kaguni, Dongchon Kang, Drosophila protease ClpXP specifically degrades DmLRPPRC1 controlling mitochondrial mRNA and translation, SCIENTIFIC REPORTS, 10.1038/s41598-017-08088-6, 7, 2017.08.
5. Keisuke Monji, Takeshi Uchiumi, Saki Hoshizawa, Mikako Yagi, Matsumoto, Takashi, Daiki Setoyama, Yuichi Matsushima*, Gotoh Kazuhito, Rie Amamoto, Dongchon Kang, Serum depletion induced cancer stem cell-like phenotype due to nitric oxide synthesis in oncogenic HRas transformed cells, ONCOTARGET, 10.18632/oncotarget.12117, 7, 46, 75221-75234, 2016.11.
6. Chika Sakai, Yamaguchi, Seiji, Masayuki Sasaki, Yusaku Miyamoto, Yuichi Matsushima*, Yu-ichi Goto, ECHS1 Mutations Cause Combined Respiratory Chain Deficiency Resulting in Leigh Syndrome, HUMAN MUTATION, 10.1002/humu.22730, 36, 2, 232-239, 2015.02, 脂肪酸代謝酵素の異常は脂肪酸代謝異常症をていするが、本論文では脂肪酸代謝酵素の一つであるECHS1が、ミトコンドリア病の原因遺伝子であることを明らかにした。また、ECHS1の異常がが脂肪酸代謝異常を引き起こすだけでなく、ミトコンドリアの呼吸鎖活性の低下をしめすことを明らかにした。また、ECHS1変異が呼吸鎖複合体を阻害する代謝物の蓄積を引き起こしミトコンドリア病に至る可能性を示した。.
7. Masamune Aihara, Xiulian Jin, Yusuke Kurihara, Yuichi Matsushima, Masahide Oku, Yuko Hirota, Tetsu Saigusa, Yoshimasa Aoki,, Takeshi Uchiumi, Yasuyoshi Sakai, Dongchon Kang, Tomotake KANKI, The Tor and Sin3-Rpd3 complex regulate expression of the mitophagy receptor protein Atg32, J. Cell Sci., 10.1242/​jcs.153254, 2014.05.
8. Miguel Fernandez-Moreno A, Rosana Hernandez, Cristina Adan, Marina Roberti, Francesco Bruni, Paola Loguercio Polosa, Palmiro Cantatore, Yuichi Matsushima, Laurie S KagunI, Rafael Garesse, Drosophila nuclear factor DREF regulates the expression of the mitochondrial DNA helicase and mitochondrial transcription factor B2 but not the mitochondrial translation factor B1, BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 10.1016/j.bbagrm.2013.07.006, 1829, 10, 1136-1146, 2013.10.
9. Shimazaki H, Takiyama Y, Ishiura H, Sakai C, Matsushima Y, Hatakeyama H, Honda J, Sakoe K, Naoi T, Namekawa M, Fukuda Y, Takahashi Y, Goto J, Tsuji S, Goto Y, Nakano I, A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55). , J Med Genet, 49, 23, 777-784, 2012.12.
10. Sanchez-Martinez A, Calleja M, Peralta S, Matsushima Y, Hernandez-Sierra R, Whitworth AJ, Kaguni LS, Garesse R, Modeling pathogenic mutations of human twinkle in Drosophila suggests an apoptosis role in response to mitochondrial defects., PLoS One, 7, 8, e43954, 2012.08.
11. Peralta S, Clemente P, Sanchez-Martinez A, Calleja M, Hernandez-Sierra R, Matsushima Y, Adan C, Ugalde C, Fernandez-Moreno MA, Kaguni LS, Garesse R, Coiled-Coil Domain Containing protein 56 (CCDC56) is a novel mitochondrial protein essential for cytochrome c oxidase function. , J Biol Chem, 287, 29, 24174-24185, 2012.07.
12. Furukawa R, Yamada Y, Matsushima Y*, Goto Y, Harashima H, The manner in which DNA is packaged with TFAM has an impact on transcription activation and inhibition., FEBS Open Bio, 2, 145-150, 2012.06.
13. Matsushima Y, Goto Y, Kaguni LS, Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM). , Proc Natl Acad Sci USA, 107, 43, 18410-18415, 2010.10.
14. Yuichi Matsushima, Laurie S Kaguni, Functional importance of the conserved N-terminal domain of the mitochondrial replicative DNA helicase, BBA-Bioenergetics, 1787, 5, 290-295, 2009.05.
15. Matsushima Y, Farr CL, Fan L, Kaguni LS, Physiological and biochemical defects in carboxyl-terminal mutants of mitochondrial DNA helicase. , J Boil Chem, 283, 35, 23964-23971, 2008.08.
16. Adan C, Matsushima Y, Hernandez-Sierra R, Marco-Ferreres R, Fernandez-Moreno MA, Gonzalez-Vioque E, Calleja M, Aragon JJ, Kaguni LS, Garesse R, Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development., J Boil Chem, 283, 18, 12333-12342, 2008.05.
17. Matsushima Y, Kaguni LS, Differential phenotypes of active site and human autosomal dominant progressive external ophthalmoplegia mutations in drosophila mitochondrial DNA helicase expressed in Schneider cells. , J Boil Chem, 280, 17, 16815-16820, 2007.03.
18. Matsushima Y, Adan C, Garesse R, Kaguni LS, Drosophila mitochondrial transcription factor B1 modulates mitochondrial translation but not transcription or DNA copy number in Schneider cells. , J Boil Chem, 282, 13, 9436-9444, 2005.03.
19. Matsushima Y, Garesse R, Kaguni LS, Drosophila mitochondrial transcription factor B2 regulates mitochondrial DNA copy number and transcription in Schneider cells. , J Boil Chem, 279, 26, 26900-26905, 2004.06.
20. Farr CL, Matsushima Y, Lagina AT, 3rd, Luo N, Kaguni LS, Physiological and biochemical defects in functional interactions of mitochondrial DNA polymerase and DNA-binding mutants of single-stranded DNA-binding protein., J Boil Chem, 279, 17, 17047-17053, 2004.04.
21. Matsushima Y, Matsumura K, Ishii S, Inagaki H, Suzuki T, Matsuda Y, Beck K, Kitagawa Y, Functional domains of chicken mitochondrial transcription factor a for the maintenance of mitochondrial DNA copy number in lymphoma cell line DT40. , J Boil Chem, 278, 33, 31149-31158, 2003.08.
22. Goto A, Matsushima Y, Kadowaki T, Kitagawa Y, Drosophila mitochondrial transcription factor a (d-tfam) is dispensable for the transcription of mitochondrial DNA in kc167 cells., Biochem J, 354, 1, 243-248, 2001.03.
23. Inagaki H, Hayashi T, Matsushima Y, Lin KH, Maeda S, Ichihara S, Kitagawa Y, Saito T, Isolation of rat mitochondrial transcription factor a (r-Tfam) cDNA. DNA sequence, DNA sequence, 11, 1-2, 131-135, 2000.02.
24. Okumara K, Nogami M, Matsushima Y, Matsumura K, Nakamura K, Taguchi H, Kitagawa Y, Mapping of human DNA-binding nuclear protein (NP220) to chromosome band 2p13.1-p13.2 and its relation to matrin 3. , Biosci Biotech Biochem , 62, 8, 1640-1642, 1998.08.
25. Matsushima Y, Nagabukuro A, Matsuda Y, Kitagawa Y, Cloning and genomic mapping of the mouse matrin 3 gene and its pseudogenes. , Cytogenet Cell Genet, 81, 3-4, 194-198, 1998.03.
26. Matsushima Y, Matsumura K, Kitagawa Y, Zinc finger-like motif conserved in a family of RNA binding proteins. , Biosci Biotech Biochem, 61, 5, 905-906, 1997.05.
27. Inagaki H, Matsushima Y, Ohshima M, Kitagawa Y, Interferons suppress mitochondrial gene transcription by depleting mitochondrial transcription factor A (mtTFA)., J Interferon Cytokine Res, 17, 5, 263-269, 1997.05.
28. Matsushima Y, Ohshima M, Sonoda M, Kitagawa Y, A family of novel DNA-binding nuclear proteins having polypyrimidine tract-binding motif and arginine/serine-rich motif. , Biochem Biophys Res Commun , 223, 2, 427-433, 1996.06.
29. Inagaki H, Matsushima Y, Nakamura K, Ohshima M, Kadowaki T, Kitagawa Y, A large DNA-binding nuclear protein with RNA recognition motif and serine/arginine-rich domain., J Boil Chem, 271, 21, 12525-12531, 1996.05.