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Nixing immaturity in red blood cells
May 05, 2008A process of self-digestion called autophagy prompts the maturation of red blood cells. Without a protein called Nix, the cells would not effectively rid themselves of organelles called mitochondria and consequently become short-lived, leading to anemia, said researchers at Baylor College of Medicine in Houston in a report that appears online today in the journal Nature.
"It's changed our thinking on autophagy," said Dr. Jin Wang, assistant professor of immunology at BCM and senior author of the report. During autophagy, the cell forms an envelope or vesicle around components of the cell that need to be degraded and removed. The vesicle then fuses with a cellular component called a lysosome that degrades its contents. The inclusion of components in the cell by autophagy vesicles was generally considered to be nonspecific.
"This is not a random process," said Wang. "Nix is instructing the cell to get rid of these mitochondria."
Nix accomplishes this task by disrupting the mitochondrial membrane potential (represented by difference in voltage across the inner membrane of the mitochondria. The interior is negative and the outside positive. The difference generates a force that drives the synthesis of ATP, the cell's energy molecule).
"We think the finding is not limited to the clearance of mitochondria in red blood cells," said Wang. "When other cells get old or stressed, their organelles may become damaged and need to be cleared by autophagy for quality control. If the cells lack such quality controls, they might have problems that result in aging, cancer and neurodegenerative diseases."
"It helps get rid of old or damaged mitochondria," he said. "It is a way to keep the cell functioning without going through programmed cell death (apoptosis)."
"Such specific regulation of autophagy may also be important for cell types in the muscle, brain and pancreas," said Dr. Min Chen, assistant professor of immunology at BCM and a corresponding author of this work. "The next step is to identify proteins interacting with Nix for mitochondrial quality control by autophagy". Other factors may also regulate this process in addition to Nix, said Hector Sandoval, a BCM graduate student who is the first author of this paper.
Baylor College of Medicine
Nix accomplishes this task by disrupting the mitochondrial membrane potential (represented by difference in voltage across the inner membrane of the mitochondria. The interior is negative and the outside positive. The difference generates a force that drives the synthesis of ATP, the cell's energy molecule).
"We think the finding is not limited to the clearance of mitochondria in red blood cells," said Wang. "When other cells get old or stressed, their organelles may become damaged and need to be cleared by autophagy for quality control. If the cells lack such quality controls, they might have problems that result in aging, cancer and neurodegenerative diseases."
"It helps get rid of old or damaged mitochondria," he said. "It is a way to keep the cell functioning without going through programmed cell death (apoptosis)."
"Such specific regulation of autophagy may also be important for cell types in the muscle, brain and pancreas," said Dr. Min Chen, assistant professor of immunology at BCM and a corresponding author of this work. "The next step is to identify proteins interacting with Nix for mitochondrial quality control by autophagy". Other factors may also regulate this process in addition to Nix, said Hector Sandoval, a BCM graduate student who is the first author of this paper.
Baylor College of Medicine
Autophagy Current Events and Autophagy News RSSCancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer
Agios Pharmaceuticals today announced that its scientists have established, for the first time, that the mutated IDH1 gene has a novel enzyme activity consistent with a cancer-causing gene, or oncogene.
Inhibitor of heat shock protein is a potential anticancer drug, Penn study finds
Like yoga for office drones, cells do have coping strategies for stress. Heat, lack of nutrients, oxygen radicals - all can wreak havoc on the delicate internal components of a cell, potentially damaging it beyond repair.
HIV uses autophagy for its own means
Not satisfied with simply thwarting its host's defensive maneuvers, HIV actually twists one to its advantage, based on new findings from Kyei et al. in the July 27, 2009 issue of the Journal of Cell Biology (www.jcb.org). Vojo Deretic and colleagues suggest that autophagy-a stress response process-helps HIV to proliferate and that conversely, blocking autophagy lessens HIV production.
Waste disposal protein is mechanism behind cancer tumor suppression
"Taking out the trash" takes on a whole new meaning, as investigators at The Cancer Institute of New Jersey (CINJ) and Rutgers, The State University of New Jersey, have discovered that a waste disposal protein is the key to cancer tumor suppression in a process known as autophagy.
Scientists advance safety of nanotechnology
Scientists have identified for the first time a mechanism by which nanoparticles cause lung damage and have demonstrated that it can be combated by blocking the process involved, taking a step toward addressing the growing concerns over the safety of nanotechnology.
Muscle atrophy through thick but not thin
During desperate times, such as fasting, or muscle wasting that afflicts cancer or AIDS patients, the body cannibalizes itself, atrophying and breaking down skeletal muscle proteins to liberate amino acids.
Enhancing the effects of the drug used to treat chronic myeloid leukemia
Individuals with chronic myeloid leukemia (CML) are first treated with a drug known as imatinib mesylate. Although very effective, as the disease progresses it often becomes resistant to the drug.
Therapeutic effect of imatinib improved with addition of chloroquine
The therapeutic effects of the blockbuster leukemia drug imatinib may be enhanced when given along with a drug that inhibits a cell process called autophagy, researchers from the Kimmel Cancer Center at Jefferson reported in the Journal of Clinical Investigation.
TB breakthrough could lead to stronger vaccine
A breakthrough strategy to improve the effectiveness of the only tuberculosis vaccine approved for humans provided superior protection against the deadly disease in a pre-clinical test, report scientists at The University of Texas Health Science Center at Houston in Nature Medicine's Advance Online Publication March 1.
Self-digestion as a means of survival
In times of starvation, cells tighten their belts: they start to digest their own proteins and cellular organs. The process - known as autophagy - takes place in special organelles called autophagosomes.
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Autophagy in Mammalian Systems, Volume 452: Part B (Methods in Enzymology) by Daniel Klionsky (Editor) Particularly in times of stress, like starvation and disease, higher organisms have an internal mechanism in their cells for chewing up and recycling parts of themselves. The process of internal "house-cleaning" in the cell is called autophagy - literally self-eating. Breakthroughs in understanding the molecular basis of autophagy came after the cloning of ATG1 in yeast. These ATG genes in yeast were the stepping stones to the explosion of research into the molecular analysis of autophagy in higher eukaryotes. In the future, this research will help to design clinical approaches that can turn on autophagy and halt tumor growth. In this volume, a robust slate of methods for conducting research are presented, establishing a consensus of appropriate criteria for monitoring autophagy.... |
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Autophagosome and Phagosome (Methods in Molecular Biology) by Vojo Deretic (Editor) Autophagy and phagocytosis are distinct yet partially morphologically similar processes. In "Autophagosome and Phagosome", authoritative scientists present easy-to-follow methods on autophagy, a rapidly growing field with a need for standards of assessment, and phagocytosis, a relatively mature field which could benefit greatly from updated methods, in order to prompt further explorations of their similarities and differences. The methods on autophagy allow the reader to find appropriate techniques to identify, monitor, and quantify autophagic processes, while the methods devoted to phagocytosis provide researchers with several modern techniques for in vitro and in vivo studies of phagosomal organelles. Comprehensive and forward-thinking, "Autophagosome and Phagosome" offers a valuable... |
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Autophagy in Disease and Clinical Applications, Volume 453: Part C (Methods in Enzymology) by Daniel Klionsky (Editor) The third and final installment of Daniel J. Klionsky's new three-volume treatment of autophagy, this volume focuses on monitoring autophagy with regard to disease connections, and presents methods that can be used to analyze autophagy in clinical samples. Edited by one of the leading authorities in the field, this volume and its companion volumes, Autophagy: Lower Eukaryotes and Autophagy in Mammalian Systems, provide a comprehensive overview of the techniques involved in studying autophagy in eukaryotes and simple animal systems, mammalian cells and non-human animals, and humans. Particularly in times of stress, like starvation and disease, higher organisms have an internal mechanism in their cells for chewing up and recycling parts of themselves. The process of internal "house... |
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Autophagy by Landes Bioscience % Jesse | |
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Autophagy in Immunity and Infection: A Novel Immune Effector by Vojo Deretic (Editor) This first book to cover this new topic at the interface of cell biology, immunology and infection biology offers a unique insight as to how the innate and possibly the adaptive immune system are shaped by cellular mechanisms. Following a comprehensive introduction to autophagy, the work features cellular mechanisms and medical implications, structured according to all major pathogens, while also covering emerging infectious diseases, such as tuberculosis. Edited by one of the authors of a groundbreaking paper on this topic. |
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Autophagy: Lower Eukaryotes and Non-Mammalian Systems, Volume 451: Part A (Methods in Enzymology) by Daniel Klionsky (Editor) This is the companion volume to Daniel Klionsky's Autophagy: Lower Eukaryotes, which features the basic methods in autophagy covering yeasts and alternative fungi (aspergillus, podospora, magnaporthe). Klionsky is one of the leading authorities in the field. He is the editor-in-chief of Autophagy. The November 2007 issue of Nature Reviews highlighted his article, "Autophagy: from phenomenology to molecular understanding in less than a decade." He is currently editing guidelines for the field, with 230 contributing authors, that will publish in Autophagy. Particularly in times of stress, like starvation and disease, higher organisms have an internal mechanism in their cells for chewing up and recycling parts of themselves. The process of internal "house-cleaning" in the cell is... |
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Autophagy (Molecular Biology Intelligence Unit) by Daniel J. Klionsky (Author) Univ. of Michigan, Ann Arbor. Discusses autophagy and its link to cancer, cardiomyopathy, and neurodegenerative diseases. Covers all areas of autophagy, including research in animal cells, yeast, Drosphilia, and C. elegans. For researchers. | |
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Autophagy in Infection and Immunity (Current Topics in Microbiology and Immunology) by Beth Levine (Editor), Tamotsu Yoshimori (Editor), Vojo Deretic (Editor) Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy’s ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy’s roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis;... |
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Apoptosis: Methods and Protocols, Second Edition (Methods in Molecular Biology) by Peter Erhardt (Editor), Ambrus Toth (Editor) The ability to detect and quantify apoptosis, to understand its biochemistry, and to identify its regulatory genes and proteins is crucial to biomedical research. In Apoptosis: Methods and Protocols, Second Edition, expert researchers describe the techniques to best investigate the critical steps involved in the apoptotic process. Presented from several different research perspectives, the volume contains sections covering detection of apoptosis, detection of non-apoptotic cell death, modifications of apoptotic proteins during apoptosis, the analysis of its major regulators, as well as analysis of apoptosis in different organs and in model organisms. Written in the highly successful Methods in Molecular Biology™ series format, chapters include introductions to their respective... |
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