The Experts below are selected from a list of 254709 Experts worldwide ranked by ideXlab platform

Noboru Mizushima - One of the best experts on this subject based on the ideXlab platform.

  • autophagy assays for biological discovery and therapeutic development
    Trends in Biochemical Sciences, 2020
    Co-Authors: Noboru Mizushima, Leon Murphy
    Abstract:

    Autophagy is a lysosome-dependent intracellular Degradation System required for various physiological processes and can be dysregulated in human disease. To understand its biological significance and underlying mechanisms, measuring autophagic activity (i.e., autophagic flux) is critical. However, navigating which assays to use, and when, is complicated and at times the results are often interpreted inappropriately. This review will summarize both advantages and disadvantages of currently available methods to monitor autophagy. In addition, we discuss how these assays should be used in high-throughput screens to identify autophagy-modulating drugs and genes and the general features needed for biomarkers to assess autophagy in humans.

  • autophagy in protein and organelle turnover
    Cold Spring Harbor Symposia on Quantitative Biology, 2011
    Co-Authors: Noboru Mizushima
    Abstract:

    Macroautophagy is an evolutionarily conserved Degradation System in the cell. In autophagy, intracellular components are sequestered by autophagosomes and subsequently degraded upon fusion with lysosomes. Genetic analysis of autophagy in mammals has revealed that autophagy is important for various physiological processes, such as adaptive responses to starvation, embryogenesis, quality control of intracellular proteins and organelles, tumor suppression, Degradation of intracellular pathogens, and anti-aging. In this review I describe the various roles of autophagy, with a particular focus on the turnover of cytoplasmic proteins and organelles.

  • physiological role of autophagy as an intracellular recycling System with an emphasis on nutrient metabolism
    Seminars in Cell & Developmental Biology, 2010
    Co-Authors: Akiko Kuma, Noboru Mizushima
    Abstract:

    Autophagy is a major intracellular Degradation System in which the cytoplasmic contents are degraded in the lysosome. Its fundamental and evolutionarily conserved role is adaptation to starvation. Recent studies using autophagy-defective mutants of various organisms including mammals have indeed demonstrated the importance of autophagy during starvation; however, the exact mechanism underlying this beneficial effect remains unclear. In addition, it is now apparent that autophagy is also important for cellular homeostasis even under non-starvation conditions, and both non-selective and selective types of autophagy appear to be critical for this function. Here, we discuss the role of this catabolic pathway in recycling intracellular components, with particular reference to nutrient metabolism.

  • autophagy process and function
    Genes & Development, 2007
    Co-Authors: Noboru Mizushima
    Abstract:

    Autophagy is an intracellular Degradation System that delivers cytoplasmic constituents to the lysosome. Despite its simplicity, recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, which are sometimes complex. Autophagy consists of several sequential steps—sequestration, transport to lysosomes, Degradation, and utilization of Degradation products—and each step may exert different function. In this review, the process of autophagy is summarized, and the role of autophagy is discussed in a process-based manner.

  • generation of cell lines with tetracycline regulated autophagy and a role for autophagy in controlling cell size
    FEBS Letters, 2006
    Co-Authors: Nao Hosokawa, Yukichi Hara, Noboru Mizushima
    Abstract:

    Autophagy is an intracellular bulk Degradation System. We established mouse fibroblast lines coupling the Tet-off System with an Atg5−/− mouse embryonic fibroblast line to artificially regulate autophagic ability. In the presence of doxycycline (Dox), Atg5 expression was completely suppressed and these cells were autophagy-defective. After removal of Dox, autophagic ability was restored within 6 h. Very low levels of Atg5 could induce an autophagy competent state. We applied this novel System to examine the contribution of autophagy to controlling cell size. Cell size reduction in response to starvation was significantly inhibited in cells unable to undergo autophagy. The generated cell lines will be useful reagents for future mechanistic studies into the regulation and physiologic significance of autophagy.

Jan-hendrik S. Hofmeyr - One of the best experts on this subject based on the ideXlab platform.

James J Collins - One of the best experts on this subject based on the ideXlab platform.

  • Tunable protein Degradation in bacteria
    Nature Biotechnology, 2014
    Co-Authors: D Ewen Cameron, James J Collins
    Abstract:

    An orthogonal protein Degradation System in bacteria provides control of both protein concentration and the protein Degradation rate. Tunable control of protein Degradation in bacteria would provide a powerful research tool. Here we use components of the Mesoplasma florum transfer-messenger RNA System to create a synthetic Degradation System that provides both independent control of steady-state protein level and inducible Degradation of targeted proteins in Escherichia coli . We demonstrate application of this System in synthetic circuit development and control of core bacterial processes and antibacterial targets, and we transfer the System to Lactococcus lactis to establish its broad functionality in bacteria. We create a 238-member library of tagged essential proteins in E. coli that can serve as both a research tool to study essential gene function and an applied System for antibiotic discovery. Our synthetic protein Degradation System is modular, does not require disruption of host Systems and can be transferred to diverse bacteria with minimal modification.

  • Tunable protein Degradation in bacteria
    Nature biotechnology, 2014
    Co-Authors: D Ewen Cameron, James J Collins
    Abstract:

    Tunable control of protein Degradation in bacteria would provide a powerful research tool. Here we use components of the Mesoplasma florum transfer-messenger RNA System to create a synthetic Degradation System that provides both independent control of steady-state protein level and inducible Degradation of targeted proteins in Escherichia coli. We demonstrate application of this System in synthetic circuit development and control of core bacterial processes and antibacterial targets, and we transfer the System to Lactococcus lactis to establish its broad functionality in bacteria. We create a 238-member library of tagged essential proteins in E. coli that can serve as both a research tool to study essential gene function and an applied System for antibiotic discovery. Our synthetic protein Degradation System is modular, does not require disruption of host Systems and can be transferred to diverse bacteria with minimal modification.

Ben Loos - One of the best experts on this subject based on the ideXlab platform.

Tamotsu Yoshimori - One of the best experts on this subject based on the ideXlab platform.

  • Autophagy and autophagy-related proteins in the immune System
    Nature Immunology, 2015
    Co-Authors: Shusaku T Shibutani, Christian Münz, Heike Nowag, Tatsuya Saitoh, Tamotsu Yoshimori
    Abstract:

    Autophagy is an essential intracellular Degradation process. Yoshimori and colleagues review the broad role of autophagy in immunological function. Autophagy is an intracellular bulk Degradation System that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In addition, studies have revealed other roles for the autophagic machinery beyond autophagy. In this Review, we introduce advances in the knowledge of the roles of autophagy and its components in immunity, including innate immunity, inflammatory responses and adaptive immunity.

  • Autophagy and autophagy-related proteins in the immune System
    Nature immunology, 2015
    Co-Authors: Shusaku Shibutani, Christian Münz, Heike Nowag, Tatsuya Saitoh, Tamotsu Yoshimori
    Abstract:

    Autophagy is an intracellular bulk Degradation System that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In addition, studies have revealed other roles for the autophagic machinery beyond autophagy. In this Review, we introduce advances in the knowledge of the roles of autophagy and its components in immunity, including innate immunity, inflammatory responses and adaptive immunity.

  • Autophagosome formation in response to intracellular bacterial invasion.
    Cellular microbiology, 2014
    Co-Authors: Shusaku Shibutani, Tamotsu Yoshimori
    Abstract:

    Autophagy is an intracellular bulk Degradation System in which double-membrane vesicles, called autophagosomes, engulf cytoplasmic components and later fuse with lysosomes to degrade the autophagosome content. Although autophagy was initially thought a non-selective process, recent studies have clarified that it can selectively target intracellular bacteria and function as an intracellular innate immune System that suppresses bacterial survival. A key mechanism for the recognition of cytosol-invading bacteria is ubiquitination, and the recognition of the ubiquitinated target by the autophagy machinery can be accomplished multiple ways. In this review, we discuss recent findings regarding the induction of autophagosome formation in response to intracellular bacterial invasion.

  • A current perspective of autophagosome biogenesis
    Cell Research, 2014
    Co-Authors: Shusaku T Shibutani, Tamotsu Yoshimori
    Abstract:

    Autophagy is a bulk Degradation System induced by cellular stresses such as nutrient starvation. Its function relies on the formation of double-membrane vesicles called autophagosomes. Unlike other organelles that appear to stably exist in the cell, autophagosomes are formed on demand, and once their formation is initiated, it proceeds surprisingly rapidly. How and where this dynamic autophagosome formation takes place has been a long-standing question, but the discovery of Atg proteins in the 1990's significantly accelerated our understanding of autophagosome biogenesis. In this review, we will briefly introduce each Atg functional unit in relation to autophagosome biogenesis, and then discuss the origin of the autophagosomal membrane with an introduction to selected recent studies addressing this problem.

  • Cellular defense by autophagy
    Gan to kagaku ryoho. Cancer & chemotherapy, 2008
    Co-Authors: Tamotsu Yoshimori
    Abstract:

    As an intracellular bulk Degradation System, autophagy acts for the turnover of cellular constituents and in maintaining the amino acid pool by self Degradation to survive starvation. A recent rapid expansion of the field triggered by identification of genes essential to autophagy has revealed its diverse functions other than catabolism. For example, autophagy can eliminate pathogenic bacteria invading host cells and the abnormal proteins causing neural or hepatic degenerative diseases. Therefore, autophagy is crucial for cellular defense against harmful materials inside cells.