Yoshinori Ohsumi Research Articles

基礎科学の未来: 大隅良典先生ノーベル賞受賞から考える

基礎科学の未来: 大隅良典先生ノーベル賞受賞から考える

Autophagic Dysfunction in Type 2 Diabetes Mellitus: Pathophysiology and Therapeutic Implications

Autophagy is an intracellular catabolic system by which cells degrade and recycle cytoplasmic constituents such as organelles and proteins through the lysosome-dependent path. Belgian biochemist, Christian de Duve coined the name in 1963. The identification of autophagy-related genes and finally discoveries of mechanisms for autophagy led to the award of the 2016 Nobel Prize in Medicine or Physiology to Japanese cell biologist, Yoshinori Ohsumi specializing in autophagy. Autophagy shows a crucial role in removing aggregated proteins and damaged organelles in order to conserve intracellular homeostasis. In order to control cellular homeostasis and disease states autophagy illustrates a vital role. For insulin resistant patients, insulin secretion and the mass of pancreatic β-cells is increased on account of alterations in the expression and activities of numerous proteins in β-cells. Simultaneously, autophagic activity seems to also be upgraded to adjust to the dynamic changes taking place in β-cells. Actually, faulty autophagy in β-cells recaps a number of features that are perceived in pancreatic islets in the course of the formation of type 2 diabetes mellitus (T2DM). In contrast, the dyregulation of autophagic function is also appears to happen in the β-cells of T2DM patients. Furthermore, autophagy deficiency is linked with the diabetes-related organ dysfunction. Therefore the intention of this study was to provide the impacts of autophagy based on current researches in the development of T2DM and to explore new therapeutic strategies for stopping T2DM pathogenesis.

Recycling to discover something new: the role of autophagy in kidney disease

This year, the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his groundbreaking work in dissecting the mechanisms of autophagy, a cellular process resulting in the organized degradation of cytoplasmic components. Ohsumi's work pavedthe way for subsequent studies that demonstrated critical roles for autophagy in modulating both acute and chronic kidney injury. This work may lead to future therapeutic approaches that target the autophagy system to prevent or treat kidney diseases.

Why autophagy is good for retinal ganglion cells?

Autophagy is a catabolic pathway that promotes the degradation and recycling of cellular components. Proteins, lipids, and even whole organelles are engulfed in autophagosomes and delivered to the lysosome for elimination. In response to stress, autophagy mediates the degradation of cell components, which are recycled to generate the nutrients and building blocks required to sustain cellular homeostasis. Moreover, it has an important role in cellular quality control, particularly in neurons, in which the total burden of altered proteins and damaged organelles cannot be reduced by redistribution to daughter cells through cell division. Autophagy occurs in all cells and tissues, and it is regulated by the Atg genes. The importance of this pathway has been recently recognized by the Nobel Prize in Physiology and Medicine award to Professor Yoshinori Ohsumi who was the discoverer of the first Atg genes in yeast in the 1990s. Research has only begun to examine the role of autophagy in the visual system. Both the retina and the eye are exposed to a variety of environmental insults and stressors, including genetic mutations and age-associated alterations that impair their function. Here, we review studies that have sought to explain autophagy's importance for retinal ganglion cells, and their implications for diseases like glaucoma and optic neuropathies.

Yoshinori Ohsumi's Nobel Prize for mechanisms of autophagy: from basic yeast biology to therapeutic potential.

On 3 October 2016, Japanese cell biologist Yoshinori Ohsumi was awarded the Nobel Prize in Physiology or Medicine 'for his discoveries of mechanisms for autophagy'; autophagy being an intracellular degradation pathway that helps maintain cytoplasmic homeostasis. This commentary discusses Ohsumi's Nobel prize-winning work in context, before explaining the clinical relevance of autophagy.

Autophagy Captures the Nobel Prize

This year's Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi for the discovery of the molecular principles governing autophagy, an intracellular degradation pathway routed via lysosomes or vacuoles. It is a story of a simple yet insightful yeast genetic screen that revealed the inner circuitry of one of the most powerful quality-control pathways in cells.

Nobel Prize Honors Autophagy Discovery.

Japanese cell biologist Yoshinori Ohsumi, PhD, was awarded this year's Nobel Prize in Physiology or Medicine for his discovery of autophagy. His groundbreaking studies in yeast cells illuminated how cells break down and recycle damaged material, a process that is critical to the survival of both normal cells and some cancer cells.

One 2016 Nobel: Yeast-Based Autophagy Work; 3 MacArthurs: Microbiology

The 2016 Nobel Prize in Physiology or Medicine, about $936,000 this year, recognizes Yoshinori Ohsumi of Japan for his efforts to understand autophagy, a fundamental process for degrading and recycling cellular components, research that he began by studying yeast. Separately, among the 2016 MacArthur Foundation Fellows, who receive $625,000 “genius awards,” are microbiologist Dianne Newman, who studies bacteria that played roles in shaping the Earth as well as in modern biomedical contexts; geobiologist Victoria Orphan, whose focus is on microbial communities in extreme environments; and physical biologist Manu Prakash, who invented several devices that can be used for diagnostic work in microbiology. Also noteworthy, the 2016 LaskerDeBakey Clinical Medical Research Award is shared by three scientists whose research on hepatitis C virus (HCV) led to development of drugs for treating HCV infections.

Nobel Prize in Physiology or Medicine 2016

The Nobel Prize in Physiology or Medicine 2016 was awarded to Yoshinori Ohsumi of the Tokyo Institute of TechTechnology, Tokyo, Japan 'for his discoveries of mechanisms for autophagy' (http://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/).

Yoshinori Ohsumi wins Medicine Nobel Prize

The 2016 Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi, 71, a cell biologist at Tokyo Institute of Technology “for his discoveries of mechanisms for autophagy.” Autophagy is the process by which cells capture large dysfunctional proteins, aging organelles, and invading pathogens in vesicles and then send them to the lysosome for degradation, said Juleen Zierath, chair of the Nobel Committee for Physiology or Medicine, in announcing the nearly $1 million prize. “Without autophagy, our cells won’t survive.” Dysfunction of the autophagy process is life-threatening from birth through old age. For example, autophagy is disrupted in Alzheimer’s disease, when toxic protein aggregates are not properly discarded. As a consequence, drugmakers have continued to eye the pathway as a therapeutic target. Although researchers had known since the 1960s that cells cleaned up their large cellular garbage by enclosing it in vesicle sacks and sending it to the

Nobel honors discoveries in how cells eat themselves.

Cellular sanitation helps keep diseases at bay.

会長談話「大隅良典先生のノーベル生理学・医学賞受賞を祝して」を公表

会長談話「大隅良典先生のノーベル生理学・医学賞受賞を祝して」を公表

Recent progress in autophagy

Recent progress in autophagy

Newsmakers

This week's Newsmakers are American computer scientist Ivan Sutherland and Japanese biologist Yoshinori Ohsumi, who have won the Kyoto Prize.

ATG Systems from the Protein Structural Point of View

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTATG Systems from the Protein Structural Point of ViewNobuo N. Noda†, Yoshinori Ohsumi*‡, and Fuyuhiko Inagaki*†View Author Information Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 001-0021, Japan, and Division of Molecular Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan†Hokkaido University.‡National Institute for Basic Biology.Cite this: Chem. Rev. 2009, 109, 4, 1587–1598Publication Date (Web):February 23, 2009Publication History Received26 August 2008Published online23 February 2009Published inissue 8 April 2009https://doi.org/10.1021/cr800459rCopyright © 2009 American Chemical SocietyRIGHTS & PERMISSIONSACS Editors’ ChoiceArticle Views7494Altmetric-Citations59LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-AlertsSUBJECTS:Autophagy,Chemical structure,Membranes,Molecular properties,Peptides and proteins Get e-Alerts

A Trypanosoma cruzi Phosphatidylinositol 3-Kinase (TcVps34) Is Involved in Osmoregulation and Receptor-mediated Endocytosis

Trypanosoma cruzi, the etiological agent of Chagas disease, has the ability to respond to a variety of environmental changes during its life cycle both in the insect vector and in the vertebrate host. Because regulation of transcription initiation seems to be nonfunctional in this parasite, it is important to investigate other regulatory mechanisms of adaptation. Regulatory mechanisms at the level of signal transduction pathways involving phosphoinositides are good candidates for this purpose. Here we report the identification of the first phosphatidylinositol 3-kinase (PI3K) in T. cruzi, with similarity with its yeast counterpart, Vps34p. TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate, thus confirming that it belongs to class III PI3K family. Overexpression of TcVps34 resulted in morphological and functional alterations related to vesicular trafficking. Although inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294,000, resulted in reduced regulatory volume decrease after hyposmotic stress, cells overexpressing this enzyme were resistant to these inhibitors. Furthermore, these cells were able to recover their original volume faster than wild type cells when they were submitted to severe hyposmotic stress. In addition, in TcVps34-overexpressing cells, the activities of vacuolar-H+-ATPase and vacuolar H+-pyrophosphatase were altered, suggesting defects in the acidification of intracellular compartments. Furthermore, receptor-mediated endocytosis was partially blocked although fluid phase endocytosis was not affected, confirming a function for TcVps34 in membrane trafficking. Taken together, these results strongly support that TcVps34 plays a prominent role in vital processes for T. cruzi survival such as osmoregulation, acidification, and vesicular trafficking.