Chief Scientist Laboratories Glycometabolic Biochemistry Laboratory
Chief Scientist: Tadashi Suzuki (D.Sc.)
Research Summary
Peptide:N-glycanase (PNGase) releases N-glycans from glycoproteins/glycopeptides. The cytoplasmic PNGases, ubiquitously found throughout eukaryotes, are now widely recognized as a component implicated in the ERAD (ER-associated degradation) process, which constitute one of the quality control machineries for newly synthesized misfolded glycoproteins exported out of the ER lumen. While the biosynthetic pathway for N-glycans has been clarified in detail, the catabolic pathway for the "free" N-glycans released by the cytoplasmic PNGase remains largely unknown. Although this "non-lysosomal" metabolic path for N-glycan may represent one of the very basic biological phenomena in eukaryotes, there are still many more enzymes/transporters that remains to be identified. We are currently trying to identify other players involved in this process, and also taking a number of approaches to analyze the physiological importance of this non-lysosomal metabolic pathway.
Main Research Fields
- Biological Sciences
Related Research Fields
- Biology
- Medicine, Dentistry & Pharmacy
Keywords
- glycoproteins
- Asparagine-linked glycans
- metabolism
- Peptide:N-glycanase
- NGLY1
Selected Publications
- 1.
Yoshida, Y., Takahashi, T., Ishii, N., Matsuo, I., Takahashi, S., Inoue, H., Endo, A., Tsuchiya, H., Okada, M., Ando, C., Suzuki, T., Dohmae, N., Saeki, Y., Tanaka, K., and Suzuki, T.
"Sugar-mediated non-canonical ubiquitination impairs Nrf1/NFE2L1 activation"
Mol Cell 84, 3115-3127 (2024) - 2.
Makita, Y., Asahina, M., Fujinawa, R., Yukitake, H., and Suzuki, T.
"Intranasal oxytocin suppresses seizure-like behaviors in a mouse model of NGLY1 deficiency"
Commun Biol 7, 460 (2024) - 3.
Hirayama, H., Tachida, Y., Fujinawa, R., Matsuda, Y., Murase, T., Nishiuchi, Y., and Suzuki, T.
"Development of a fluorescence and quencher-based FRET assay for detection of endogenous peptide:N-glycanase/NGLY1 activity"
J Biol Chem 300, 107121 (2024) - 4.
Huang, C., Seino, J., Honda, A., Fujihira, H., Wu, D., Okahara, K., Kitazume, S., Nakaya, S., Kitajima, K., Sato, C., and Suzuki, T.
"Rat hepatocytes secrete free oligosaccharides"
J Biol Chem 300, 105712 (2024) - 5.
Li, S.-T., Hirayama, H., Huang, C., Matsuda, T., Oka, R., Yamasaki, T., Kohda, D., and Suzuki, T.
"Hydrolytic activity of yeast oligosaccharyltransferase is enhanced when misfolded proteins accumulate in the endoplasmic reticulum"
FEBS J 291, 884-896 (2024) - 6.
Yoshida, Y., Asahina, M., Murakami, A., Kawasaki, J., Yoshida, M., Fujinawa, R., Iwai, K., Tozawa, R., Matsuda, N., Tanaka, K., and Suzuki, T.
"Loss of peptide:N-glycanase causes proteasome dysfunction mediated by a sugar-recognizing ubiquitin ligase"
Proc. Natl. Acad. Sci. USA 118, e2102902118 (2021) - 7.
Asahina, M., Fujinawa, R., Hirayama, H., Tozawa, R., Kajii, Y., and Suzuki, T.
"Reversibility of motor dysfunction in the rat model of NGLY1 deficiency"
Mol. Brain, 14, 91 (2021) - 8.
Asahina, M., Fujinawa, R.,Nakamura, S., Yokoyama, K., Tozawa, R., and Suzuki, T.
"Ngly1-/- rats develop neurodegenerative phenotypes and pathological abnormalities in their peripheral and central nervous systems"
Hum Mol. Genet. 29, 1635-1647 (2020) - 9.
Fujihira, H., Masahara-Negishi, Y., Akimoto, Y., Hirayama, H., Lee, H.-C., Story, B. A., Mueller, W. F., Jakob, P., Clauder-Munster, S., Sterinmetz, L. M., Radhakrishnan, S. K., Kawakami, H., Kamada, Y., Miyoshi, E., Yokomizo, T. and Suzuki, T.
"Liver-specific deletion of Ngly1 causes abnormal nuclear morphology and lipid metabolism under food stress"
Biochim. Biophys. Acta Mol. Basis Dis. 1866, 165588 (2020) - 10.
Hirayama, H., Matsuda, T., Tsuchiya, Y., Oka, R., Seino, J., Huang, C., Nakajima, K., Noda, Y., Shichino, Y., Iwasaki, S., and Suzuki, T.
"Free glycans derived from O-mannosylated glycoproteins suggest the presence of an O-glycoprotein degradation pathway in yeast"
J. Biol. Chem. 294, 15900-15911 (2019)* selected as "Editors' pick"
Recent Research Results
Annual research report
Related Links
Lab Members
Principal investigator
- Tadashi Suzuki
- Chief Scientist
Core members
- Masashi Ueki
- Senior Research Scientist
- Ken-ichi Moto
- Senior Research Scientist
- Katsuhiko Kamada
- Senior Research Scientist
- Hiroto Hirayama
- Research Scientist
- Haruhiko Fujihira
- Research Scientist
- Akinobu Honda
- Special Postdoctoral Researcher
- Shengtao Li
- Postdoctoral Researcher
- Keiko Sato
- Technical Staff I
- Junichi Seino
- Technical Staff I
- Yoshihito Osada
- Senior Visiting Scientist
- Shino Manabe
- Visiting Scientist
- Yoichi Takeda
- Visiting Scientist
- Ryosuke Koyama
- Visiting Scientist
- Yuko Suzuki
- Assistant
- Tsugiyo Matsuda
- Research Part-time Worker II
- Akemi Suzuki
- Research Part-time Worker II
Contact Information
S405 Bioscience Bldg,
2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Email: tsuzuki_gm@riken.jp