2016年10月04日

大隅教授の主な論文

今年のノーベル医学生理学賞の受賞が決まった大隅教授の主な論文は以下の通りです。

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主な論文

1992年
Autophagy in Yeast Demonstrated with Proteinase-Deficient Mutants and Conditions for its Induction (Takeshige, K. et al.), J. Cell Biol. 119: 301-311, 1992
1993年
Isolation and Characterization of Autophagy-Defective Mutants of Saccharomyces cerevisiae (Tsukada, M. and Ohsumi, Y.), FEBS Lett. 333: 169-174, 1993
1998年
A Protein Conjugation System Essential for Autophagy (Mizushima, N. et al.), Nature 395: 395-398, 1998
2000年
A Ubiquitin-like System Mediates Protein Lipidation (Ichimura, Y. et al.), Nature 408: 488-492, 2000
2001年
The Pre-Autophagosomal Structure Organized by Concerted Functions of APG Genes Is Essential for Autophagosome Formation (Suzuki, K. et al.), EMBO J. 20: 5971-5981, 2001
2007年
Atg8, a Ubiquitin-like Protein Required for Autophagosome Formation, Mediates Membrane Tethering and Hemifusion (Nakatogawa, H., Ichimura, Y. and Ohsumi, Y.), Cell 130: 165-178, 2007


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このうち最初の1992年の論文の概略をご紹介します。

Abstract

For determination of the physiological role and mechanism of vacuolar proteolysis in the yeast Saccharomyces cerevisiae, mutant cells lacking proteinase A, B, and carboxypeptidase Y were transferred from a nutrient medium to a synthetic medium devoid of various nutrients and morphological changes of their vacuoles were investigated. After incubation for 1 h in nutrient-deficient media, a few spherical bodies appeared in the vacuoles and moved actively by Brownian movement. These bodies gradually increased in number and after 3 h they filled the vacuoles almost completely. During their accumulation, the volume of the vacuolar compartment also increased. Electron microscopic examination showed that these bodies were surrounded by a unit membrane which appeared thinner than any other intracellular membrane. The contents of the bodies were morphologically indistinguishable from the cytosol; these bodies contained cytoplasmic ribosomes, RER, mitochondria, lipid granules and glycogen granules, and the density of the cytoplasmic ribosomes in the bodies was almost the same as that of ribosomes in the cytosol. The diameter of the bodies ranged from 400 to 900 nm. Vacuoles that had accumulated these bodies were prepared by a modification of the method of Ohsumi and Anraku (Ohsumi, Y., and Y. Anraku. 1981. J. Biol. Chem. 256:2079-2082). The isolated vacuoles contained ribosomes and showed latent activity of the cytosolic enzyme glucose-6-phosphate dehydrogenase. These results suggest that these bodies sequestered the cytosol in the vacuoles. We named these spherical bodies "autophagic bodies." Accumulation of autophagic bodies in the vacuoles was induced not only by nitrogen starvation, but also by depletion of nutrients such as carbon and single amino acids that caused cessation of the cell cycle. Genetic analysis revealed that the accumulation of autophagic bodies in the vacuoles was the result of lack of the PRB1 product proteinase B, and disruption of the PRB1 gene confirmed this result. In the presence of PMSF, wild-type cells accumulated autophagic bodies in the vacuoles under nutrient-deficient conditions in the same manner as did multiple protease-deficient mutants or cells with a disrupted PRB1 gene. As the autophagic bodies disappeared rapidly after removal of PMSF from cultures of normal cells, they must be an intermediate in the normal autophagic process. This is the first report that nutrient-deficient conditions induce extensive autophagic degradation of cytosolic components in the vacuoles of yeast cells.


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