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Fujiki Yukio Last modified date:2010.4.23



Graduate School
Undergraduate School


E-Mail
Academic Degree
Doctor of Agriculture
Field of Specialization
Molecular Cell Biology
Outline Activities
In the life sciences, our lab is most interested in study of the area covering molecular cell biology. The molecular architecture of cells provides the basis of life itself, including humans. The term “protein kinesis” in molecular cell biology describes the various aspects of how cells direct proteins to specific targets and modulate interactions among their intracellular organelles, also having relevance in understanding how the amount and localizations of particular proteins are controlled during development and in healthy and diseased cells.
To elucidate the hierarchy of highly organized biogenesis of intracellular organelles, peroxisome, a single membrane-bounded essential organelle, has been used as a model compartment in mammalian and yeast systems. Peroxisomes are present in a wide variety of eukaryotic cells, from yeast to humans, and they function in various metabolic pathways, including theÉ¿-oxidation of very long chain fatty acids and the synthesis of ether-lipids. Peroxisomal proteins, including membrane proteins, are encoded by nuclear genes and translated on free polyribosomes in the cytosol. Peroxisomes are thought to form by division of preexisting peroxisomes after the import of newly synthesized proteins. The functional consequence of human peroxisomes is highlighted by fatal genetic peroxisome biogenesis disorders (PBD), including Zellweger syndrome, neonatal adrenoleukodystrohy, and infantile Refsum disease, all of which are linked to a failure of peroxisome assembly. We identified genetic heterogeneity comprising more than 15 complementation groups in identified genetic heterogeneity comprising more than 1 complementation groups in mammals, by using patient’s fibroblasts and Chinese hamster ovary (CHO) cell mutants. Therefore, peroxisome assembly in mammals requires more than 15 genes.
Mechanisms of peroxisome assembly, including peroxisomal import of newly synthesized proteins, are one of the major foci in the peroxisome research. The successful isolation of animal cell mutants prompted us to search for the genes essential for peroxisome assembly. A cDNA encoding peroxisome assembly gactor-1 (PAF-1, peroxin Pex2p) was isolated for the first time (Nature, 1991) and shown to be a Zellweger syndrome pathogenic gene (Science, 1992). Another eight peroxin cDNAs, PEX1 (1), PEX3 (Mol. Biol. Cell, 2000, 2), PEX5 (10), PEX6 (Nature Genet., 1995), PEX12 (Nature Genet., 1997,8) PEX13 (Hum. Mol. Genet., 1999), PEX14 (5), and PEX19 (6) have been cloned by functional phenotype-complementation assay on CHO cell mutants; PEX10 (Hum. Mol. Genet., 1998) and PEX16 (7) by the expressed sequence tag search, using yeast PEXgenes. We also showed these PEXs, except for PEX14, to be responsible for human PBD (see review: ref.3). However, the biochemical functions of most of these genes (or gene products) in peroxisome biogenesis are not well understood at the molecular level. Meanwhile, we have recently demonstrated that a mobile shuttling peroxisome targeting signal 1 (PTS1)-receptor, Pex5p, carrying the PTS1 cargo proteins, docks with the initial site Pe14 in a putative import machinery, subsequently translocating to other components such as Pex13p, Pex2p, pex10p, and Pex12p, using CHO cell mutants, pex2, pex12, pex13, and pex14 (1,4). Furthermore the import of PTS2 protein and its receptor Pex7p complexes was shown to be exclusively dependent of the longer isoform, Pex5pL, of Pex5p (1, 4; J. Biol. Chem., 2002).
Our recent findings strongly suggest that Pex3p, Pex16p, and pex19p function as essential factors required for the translocation process of membrane protein and/or membrane vesicle assembly, possibly in a concerted manner (2,6,7; Mol. Biol. Cell, 2000). These observations may provide the first evidence that peroxisomes form de novo and do not have to arise from pre-existing, morphologically recognizable peroxisomes. At any event, several issues, including those regarding roles of the peroxins, Pex3p, Pex16p, and Pex19p, in assembly of membrane vesicles as well as translocations for membrane polypeptides and soluble matrix proteins, remain to be addressed at the molecular and cellular levels. Of note, we have been focusing to cloning of the remaining, last PBD pathogenic gene responsible for complementation group 8.
Research
Research Interests
  • Molecular mechanism of peroxisome biogenesis and its human disorders
    keyword : peroxisome, peroxin, peroxisome biogenesis disorders, Zellweger syndrome
    1994.04.