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Autophagosomes
An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, invading microorganisms). After formation, autophagosomes deliver cytoplasmic components to the lysosomes. The outer membrane of an autophagosome fuses with a lysosome to form an autolysosome. The lysosome's hydrolases degrade the autophagosome-delivered contents and its inner membrane. The formation of autophagosomes is regulated by genes that are well-conserved from yeast to higher eukaryotes. The nomenclature of these genes has differed from paper to paper, but it has been simplified in recent years. The gene families formerly known as APG, AUT, CVT, GSA, PAZ, and PDD are now unified as the ATG (AuTophaGy related) family. The size of autophagosomes varies between mammals and yeast. Yeast autophagosomes are about 500-900 nm, while m ...
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Autophagy
Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components. Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells. Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly. Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy. In macroautophagy (the most thoroughly researched form of autophagy), cytoplasmic components ( ...
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Macroautophagy
Autophagy (or autophagocytosis; from the Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components. Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells. Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly. Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy. In macroautophagy (the most thoroughly researched form of autophagy), cytoplasmic components (like mitochon ...
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Lysosomes
A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation center. Their primary responsibility is catabolic degradation of proteins, polysaccharides and lipids into their respective building-block molecules: amino acids, monosaccharides, and free fatty acids. The breakdown is done by various enzymes, for example proteases, glycosidases and lipases. With an acidic lumen limited by a single-bilayer lipid membrane, the lysosome holds an environment isolated from the rest of the cell. The lower pH creates optimal conditions for the over 60 different hydrolases inside. Lysosomes receive extracellular particles through endocytosis, and intracellular components through autophagy. They can also fuse with the plasma membrane and secrete their contents, a process called lysosomal exocytosis. After degradation ...
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ATG8
Autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. The transient conjugation of Atg8 to the autophagosomal membrane through a ubiquitin-like conjugation system is essential for autophagy in eukaryotes. Even though there are homologues in animals (see for example GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, MAP1LC3B2, and MAP1LC3C), this article mainly focuses on its role in lower eukaryotes such as ''Saccharomyces cerevisiae''. Structure Atg8 is a monomer of 117 aminoacids and a molecular weight of 13,6kDa. It consists of a 5-stranded β-sheet, which is enclosed by two α-helices at one side and one α-helix at the other side and exhibits a conserved GABARAP domain. Even though Atg8 does not show a clear sequence homology to ubiquitin, its crystal structure reveals a conserved ubiquitin-like fold. Function In autophagy Atg8 is one of the key molecular components involved in autophagy, the cellular pr ...
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MAP1LC3A
Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the ''MAP1LC3A'' gene. Two transcript variants encoding different isoforms have been found for this gene. Function MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. The protein encoded by this gene is one of the light chain subunits and can associate with either MAP1A or MAP1B. MAPLC3A is one of the mammalian homologues of yeast ATG8, an important marker and effector of autophagy. Regulation MAP1LC3A is regulated by several post-translational modifications. These include covalent linkage of the C-terminus to phosphatidylethanolamine in autophagic membranes, and phosphorylation by protein kinase A In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activi ...
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Atg1
AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in ''S.cerevisiae'', encoded by the gene ATG1. It is essential for the initial building of the autophagosome and Cytoplasm-to-vacuole targeting, Cvt vesicles. In a non-kinase role it is - through complex formation with Atg13 and Atg17 - directly controlled by the TOR (gene), TOR kinase, a sensor for nutrient availability. Introduction Atg1 can associate with a number of other proteins of the Atg family to form a complex that functions in autophagosome or Cvt vesicle formation. The initiation of autophagy involves the building of the pre-autophagosomal structure (PAS). Most Atg proteins accumulate at the PAS and generate either Cvt vesicles under normal growing conditions or autophagosomes under starvation. To date, there are 31 ATG genes, which can be classified into several different groups according to their functions at the different steps of the pathway. 17 of these genes only work in the Cvt pathway. Structure ...
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ATG12
Autophagy related 12 is a protein that in humans is encoded by the ''ATG12'' gene. Autophagy is a process of bulk protein degradation in which cytoplasmic components, including organelles, are enclosed in double-membrane structures called autophagosomes and delivered to lysosomes or vacuoles for degradation. ATG12 is the human homolog of a yeast protein involved in autophagy (Mizushima et al., 1998). upplied by OMIMref name="entrez"/> Autophagy requires the covalent attachment of the protein Atg12 to ATG5 through a ubiquitin-like conjugation system. The Atg12-Atg5 conjugate then promotes the conjugation of ATG8 to the lipid phosphatidylethanolamine. Atg12 was found to be involved in apoptosis. This protein promotes apoptosis through an interaction with anti-apoptotic members of the Bcl-2 family The Bcl-2 family (TC# 1.A.21) consists of a number of Conserved sequence, evolutionarily-conserved proteins that share Bcl-2 Sequence homology, homology (BH) domains. The Bcl-2 family ...
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ATG16L1
Autophagy related 16 like 1 is a protein that in humans is encoded by the ''ATG16L1'' gene. This protein is characterized as a subunit of the autophagy-related ATG12- ATG5/ATG16 complex and is essentially important for the LC3 ( ATG8) lipidation and autophagosome formation. This complex localizes to the membrane and is released just before or after autophagosome completion. Furthermore, ATG16L1 appears to have other autophagy-independent functions, e.g., intracellular membrane trafficking regulation and inflammation. Autophagy in general plays a crucial role in pathways leading to innate and adaptive immunity activation. That is why many autophagy-related proteins, including ATG16L1, their gene expression and its role in autoimmune diseases are studied in-depth nowadays. Function Autophagy is the major intracellular degradation system delivering cytoplasmic components to lysosomes, and it accounts for degradation of most long-lived proteins and some organelles. Cytoplasmic ...
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The General Autophagy Process (five Phase)
''The'' is a grammatical article in English, denoting nouns that are already or about to be mentioned, under discussion, implied or otherwise presumed familiar to listeners, readers, or speakers. It is the definite article in English. ''The'' is the most frequently used word in the English language; studies and analyses of texts have found it to account for seven percent of all printed English-language words. It is derived from gendered articles in Old English which combined in Middle English and now has a single form used with nouns of any gender. The word can be used with both singular and plural nouns, and with a noun that starts with any letter. This is different from many other languages, which have different forms of the definite article for different genders or numbers. Pronunciation In most dialects, "the" is pronounced as (with the voiced dental fricative followed by a schwa) when followed by a consonant sound, and as (homophone of the archaic pronoun ''thee'') ...
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Huntingtin
Huntingtin (Htt) is the protein coded for in humans by the ''HTT'' gene, also known as the ''IT15'' ("interesting transcript 15") gene. Mutation, Mutated ''HTT'' is the cause of Huntington's disease (HD), and has been investigated for this role and also for its involvement in long-term memory storage. It is variable in its structure, as the many Polymorphism (biology), polymorphisms of the gene can lead to variable numbers of glutamine residues present in the protein. In its wild-type (normal) form, the polymorphic locus contains 6-35 glutamine residues. However, in individuals affected by Huntington's disease (an autosomal dominant genetic disorder), the polymorphic locus contains more than 36 glutamine residues (highest reported repeat length is about 250). Its commonly used name is derived from this disease; previously, the ''IT15'' label was commonly used. The mass of huntingtin protein is dependent largely on the number of glutamine residues it has; the predicted mass is aro ...
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Axon
An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, in Vertebrate, vertebrates, that typically conducts electrical impulses known as action potentials away from the Soma (biology), nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons (pseudounipolar neurons), such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the peripheral nervous system, periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the Peripheral nervous system, peripheral and Central nervous system, central ne ...
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Neurite
A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before differentiation is complete. Neurite development The development of a neurite (neuritogenesis) requires a complex interplay of both extracellular and intracellular signals. At every given point along a developing neurite, there are receptors detecting both positive and negative growth cues from every direction in the surrounding space. The developing neurite sums together all of these growth signals in order to determine which direction the neurite will ultimately grow towards. While not all of the growth signals are known, several have been identified and characterized. Among the known extracellular growth signals are netrin, a midline chemoattractant, and semaphorin, e ...
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