Research

Study of programmed cell death

The Project Leader's Profile

YoshihideTsujimoto

Ph.D., Professor, Department of Medical Genetics, Osaka University Medical
School/Graduate School of Medicine

Project Leader
  • Yoshihide Tsujimoto, Ph.D., Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine
Research Members
  • Yutaka Eguchi, Associate Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine
  • Koei Shinzawa, Assistant Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine
  • Toshiharu Shibuya, Assistant Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine
Research Collaborators
  • Yosuke Matsuoka, Visiting Assistant Professor of GCOE, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine
  • Yusuke Imagawa, Post-Doctoral fellow
  • Zheng-Guo Cui, Post-Doctoral fellow
  • Others such as graduate students of Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine

Summary

Programmed cell death is involved in a variety of biological processes, including morphogenesis during development, cell turn over, and elimination of harmful cells. Since various diseases are also known to be associated with enhanced cell death, cell death is an important theme not only for basic biology but also for medical science. Cell death studies initially began as a study of apoptosis and since have unveiled a great deal of its molecular basis. Evidence is accumulating, however, that apoptosis is just one mechanism of cell death, and that other forms of cell death (non-apoptotic forms of cell death) also play a critical role in programmed cell death and cell death-associated diseases. We have recently identified several forms of non-apoptotic cell death, including (1) Cyclophilin D-dependent mitochondrial permeability transition-mediated necrotic death, (2) calcium-independent phospholipase A2-dependent death occurring under hypoxia conditions, and (3) autophagy-dependent death. In our laboratory, we have been studying various cell death mechanisms in mammalian cells, with hopes of continuously providing novel information, which will help in understanding the whole picture of physiological and pathological cell death. In some of the aforementioned cell death mechanisms, subcellular organella, including the mitochondria and endoplasmic reticulum, have been found to be deeply involved. The continuation of these studies will make a great contribution to understanding the overall organelle network, which is the main theme of our GCOE program.

tujimoto_e.jpg

Some of Recent Papers

  1. Nakagawa, T., Shimizu, S., Watanabe, T., Yamaguchi, O., Otsu, K., Yamagata, H., Inohara, H., Kubo, T., and Tsujimoto, Y. The mitochondrial permeability transition dependent on Cyclophilin D regulates some forms of necrotic cell death, but not apoptotic cell death. Nature 434: 652-658, 2005
  2. Shigeomi Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, K., Arakawa-Kobayashi, S., Thompson,C. B., and Tsujimoto, Y. A role of Bcl-2 family of proteins in non-apoptotic programmed cell death dependent on autophagy genes. Nature Cell Biol. 6:1221-1228, 2004
  3. Shinzawa, K. and Tsujimoto, Y. PLA2 activity is required for nuclear shrinkage in caspase-independent cell death. J. Cell Biol., 163: 1219-1230, 2003
  4. Konishi, A., Shimizu, S., Hirota, J., Takao, T., Fan, Y., Matsuoka, Y., Zhang, L., Yoneda, Y., Fujii, Y., Skoultchi, A. I., and Tsujimoto Y. Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. Cell 114: 673-688, 2003