A5056765809- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Fungal and yeast genetics research
- Polyamine Metabolism and Applications
- Studies on Chitinases and Chitosanases
- Ubiquitin and proteasome pathways
- Calcium signaling and nucleotide metabolism
- Biofuel production and bioconversion
- Toxoplasma gondii Research Studies
- Lysosomal Storage Disorders Research
- Plant Gene Expression Analysis
- Photosynthetic Processes and Mechanisms
- Biochemical and Molecular Research
- ATP Synthase and ATPases Research
- Plant nutrient uptake and metabolism
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- Amino Acid Enzymes and Metabolism
- Plant Molecular Biology Research
- Bacterial Genetics and Biotechnology
- Plant Reproductive Biology
- Peptidase Inhibition and Analysis
Tokyo Institute of Technology
2016-2025
Institute of Biophysics
2019
Chinese Academy of Sciences
2019
Meiji University
2018
National Institute for Basic Biology
2002-2017
University of Washington
2016
Princeton University
2016
Brown University
2016
Université de Strasbourg
2016
Northwestern University
2016
Macroautophagy mediates the bulk degradation of cytoplasmic components. It accounts for most long-lived proteins: constituents, including organelles, are sequestered into autophagosomes, which subsequently fuse with lysosomes, where occurs. Although possible involvement autophagy in homeostasis, development, cell death, and pathogenesis has been repeatedly pointed out, systematic vivo analysis not performed mammals, mainly because a limitation monitoring methods. To understand when occurs...
Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic constituents into the lysosome/vacuole for bulk protein degradation. This involved in preservation of nutrients under starvation condition as well normal turnover component. Aberrant autophagy has been reported several neurodegenerative disorders, hepatitis, and myopathies. Here, we generated conditional knockout mice Atg7, an essential gene yeast. Atg7 was ATG conjugation systems autophagosome formation, amino acid...
Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence a role of autophagy genes tumor suppression. The beclin 1 gene monoallelically deleted 40–75% cases human sporadic breast, ovarian, prostate cancer. Therefore, we used targeted mutant mouse model to test the hypothesis that monoallelic deletion promotes tumorigenesis. Here show heterozygous...
Autophagy in the yeast is similar to that mammalian cells. A mutant designated as apg1 (autophagy) defective accumulation of autophagic bodies vacuoles was isolated by selection using a light microscope from mutagenized proteinase‐deficient strain. In strain, which has normal vacuolar proteinases, nitrogen starvation did not induce protein degradation. The lost its viability faster than wild‐type cells during starvation. By loss first screening test, 75 other apg mutants were selected. These...
Rat LC3, a homologue of yeast Atg8 (Aut7/Apg8), localizes to autophagosomal membranes after post-translational modifications. The C-terminal fragment LC3 is cleaved immediately following synthesis yield cytosolic form called LC3-I. A subpopulation LC3-I further converted an autophagosome-associating form, LC3-II. Because conjugated with phosphatidylethanolamine (PE) by ubiquitin-like system, it has been hypothesized that modified in similar manner. Here, we show [(14)C]-ethanolamine was...
In macroautophagy, cytoplasmic components are delivered to lysosomes for degradation via autophagosomes that formed by closure of cup-shaped isolation membranes. However, how the membranes is poorly understood. We recently found in yeast a novel ubiquitin-like system, Apg12-Apg5 conjugation essential autophagy. Here we show mouse conjugate localizes embryonic stem cells. Using green fluorescent protein–tagged Apg5, revealed membrane developed from small crescent-shaped compartment. Apg5 on...
Autophagy is a bulk protein degradation process that induced by starvation. The control mechanism for induction of autophagy not well understood. We found Tor, phosphatidylinositol kinase homologue, involved in the yeast, Saccharomyces cerevisiae. When rapamycin, an inhibitor Tor function, added, even cells growing nutrient-rich medium. A temperature-sensitivetor mutant also leads to at nonpermissive temperature. These results indicate negatively regulates autophagy. first molecule...
For determination of the physiological role and mechanism vacuolar proteolysis in yeast Saccharomyces cerevisiae, mutant cells lacking proteinase A, B, carboxypeptidase Y were transferred from a nutrient medium to synthetic devoid various nutrients morphological changes their vacuoles investigated. After incubation for 1 h nutrient-deficient media, few spherical bodies appeared moved actively by Brownian movement. These gradually increased number after 3 they filled almost completely. During...
Autophagy is a membrane trafficking to vacuole/lysosome induced by nutrient starvation. In Saccharomyces cerevisiae, Tor protein, phosphatidylinositol kinase-related kinase, involved in the repression of autophagy induction largely unknown mechanism. Here, we show that protein kinase activity Apg1 enhanced starvation or rapamycin treatment. addition, have also found Apg13, which binds and activates Apg1, hyperphosphorylated Tor-dependent manner, reducing its affinity Apg1. This Apg1–Apg13...
Autophagy is a bulk degradation process in eukaryotic cells; autophagosomes enclose cytoplasmic components for the lysosome/vacuole. Autophagosome formation requires two ubiquitin-like conjugation systems, Atg12 and Atg8 which are tightly associated with expansion of autophagosomal membrane. Previous studies have suggested that there hierarchy between these systems; system located upstream context Atg protein organization. However, concrete molecular relationship unclear. Here, we show using...
Vps30p/Apg6p is required for both autophagy and sorting of carboxypeptidase Y (CPY). Although Vps30p known to interact with Apg14p, its precise role remains unclear. We found that two proteins copurify Vps30p. They were identified by mass spectrometry be Vps38p Vps34p, a phosphatidylinositol (PtdIns) 3–kinase. Vps38p, Vps15p, an activator coimmunoprecipitated These results indicate functions as subunit Vps34 PtdIns 3–kinase complex(es). Phenotypic analyses indicated Apg14p are each CPY...
Autophagy and the Cvt pathway are examples of nonclassical vesicular transport from cytoplasm to vacuole via double-membrane vesicles. Apg8/Aut7, which plays an important role in formation such vesicles, tends bind membranes spite its hydrophilic nature. We show here that nature association Apg8 with changes depending on a series modifications protein itself. First, carboxy-terminal Arg residue newly synthesized is removed by Apg4/Aut2, novel cysteine protease, Gly becomes now designated...
We characterized Apg8/Aut7p essential for autophagy in yeast. Apg8p was transcriptionally upregulated response to starvation and mostly existed as a protein bound membrane under both growing conditions. Immunofluorescence microscopy revealed that the intracellular localization of changed drastically after shift starvation. resided on unidentified tiny dot structures dispersed cytoplasm at phase. During starvation, it localized large punctate structures, some which were confirmed be...