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title_seika01

HOME Activities Molecular Genetics

1.Background of research

Autophagy is a cellular degradation system in which cytoplasmic components including organelles are sequestered by double membrane structures called autophagosomes and sequestered materials are degraded by lysosomal hydrolases for supply of amino acids and for cellular homeostasis. The autophagy induced in response to nutrient deprivation is executed in a non-selective fashion, and adaptation to nutrient-poor conditions is the main purpose of autophagy. On the other hand, recent studies have shed light on another indispensable role for starvation-independent or constitutive autophagy in cellular homeostasis, which is mediated by selective degradation of specific substrate(s).

2.Research objectives

We aim to clarify the pathophysiological roles of selective autophagy as well as the molecular mechanisms.

3.Research characteristics (incl. originality and creativity)

Based on our strong expertise in protein biochemistry and mouse genetic study, we relentlessly pursue a revolutionary approach to the understanding of the role of selective autophagy in suppression of tissue degeneration and other human disease such as cancer or neurodegeneration.

4.Anticipated effects and future applications of research

Our further studies would provide us with important clues towards a new therapeutic approach against various human diseases, such as neurodegeneration, cancer and metabolic disorders.
You can see detailed information about our research on our web site.

References

  • Kageyama et al., Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway. J. Biol. Chem., vol. 289, 24944-55, 2014
  • Ichimura, Y., et al., Phosphorylation of p62 Activates the Keap1-Nrf2 Pathway during Selective Autophagy. Mol. Cell, vol. 51, 618-631, 2013
  • Mizushima, N. & Komatsu, M. Autophagy: Renovation of cells and tissues. Cell, vol. 147, 728–41, 2011
  • Inami, Y., et al., Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells. J. Cell Biol., vol. 193, 275–84, 2011
  • Takamura, A., et al., Autophagy-deficient mice develop multiple liver tumors. Genes Dev., vol. 25, 795–800, 2011
  • Komatsu, M., et al., The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through Keap1-inactivation. Nat. Cell Biol., vol. 12, 213–23, 2010
  • Komatsu, M., et al., Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell, vol. 131, 1149–63, 2007
  • Komatsu, M., et al., Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration. Proc. Natl. Acad. Sci. U S A., vol. 104, 14489–94, 2007
  • Komatsu, M., et al., Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature, vol. 441, 880–4, 2006
  • Komatsu, M., et al., Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol., vol.169, 425–34, 2005

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