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Biochimica Et Biophysica Acta Aug 2003Mitochondrial fusion has been observed in a great variety of organisms from yeast to man. It serves to mix and unify the mitochondrial compartment and plays roles in... (Review)
Review
Mitochondrial fusion has been observed in a great variety of organisms from yeast to man. It serves to mix and unify the mitochondrial compartment and plays roles in cellular aging, cell development, energy dissipation and mitochondrial DNA inheritance. Large GTPases in the mitochondrial outer membrane, termed Fzo or mitofusins, have been identified as key components of the mitochondrial fusion machinery in yeast, flies and mammalian cells. Recent studies in yeast suggest an involvement of a dynamin-related protein in the intermembrane space. Additional components have been identified by genetic screens. These findings suggest a unique and evolutionarily conserved mechanism for mitochondrial membrane fusion.
Topics: Animals; Drosophila Proteins; Fungi; GTP Phosphohydrolases; Humans; Membrane Fusion; Membrane Proteins; Mitochondria
PubMed: 12914960
DOI: 10.1016/s0167-4889(03)00091-0 -
Biochimica Et Biophysica Acta.... Nov 2022Mammarenaviruses include many significant worldwide-widespread human pathogens, among them Lassa virus (LASV), having a dramatic morbidity and mortality rate. They are a...
Mammarenaviruses include many significant worldwide-widespread human pathogens, among them Lassa virus (LASV), having a dramatic morbidity and mortality rate. They are a potential high-risk menace to the worldwide public health since there are no treatments and there is a high possibility of animal-to-human and human-to-human viral transmission. These viruses enter into the cells by endocytosis fusing its membrane envelope with the late endosomal membrane thanks to the glycoprotein GP2, a membrane fusion protein of class I. This protein contains different domains, among them the N-terminal fusion peptide (NFP), the internal fusion loop (IFL), the membrane proximal external region (MPER) and the transmembrane domain (TMD). All these domains are implicated in the membrane fusion process. In this work, we have used an all-atom molecular dynamics study to know the binding of these protein domains with a complex membrane mimicking the late endosome one. We show that the NFP/IFL domain is capable of spontaneously inserting into the membrane without a significant change of secondary structure, the MPER domain locates at the bilayer interface with an orientation parallel to the membrane surface and tends to interact with other MPER domains, and the TMD domain tilts inside the bilayer. Moreover, they predominantly interact with negatively charged phospholipids. Overall, these membrane-interacting domains would characterise a target that would make possible to find effective antiviral molecules against LASV in particular and Mammarenaviruses in general.
Topics: Animals; Endosomes; Humans; Lassa virus; Membrane Fusion; Peptides; Virus Internalization
PubMed: 35964711
DOI: 10.1016/j.bbamem.2022.184031 -
Seminars in Cell & Developmental Biology Dec 2016Poxviruses comprise a large family of enveloped DNA viruses that infect vertebrates and invertebrates. Poxviruses, unlike most DNA viruses, replicate in the cytoplasm... (Review)
Review
Poxviruses comprise a large family of enveloped DNA viruses that infect vertebrates and invertebrates. Poxviruses, unlike most DNA viruses, replicate in the cytoplasm and encode enzymes and other proteins that enable entry, gene expression, genome replication, virion assembly and resistance to host defenses. Entry of vaccinia virus, the prototype member of the family, can occur at the plasma membrane or following endocytosis. Whereas many viruses encode one or two proteins for attachment and membrane fusion, vaccinia virus encodes four proteins for attachment and eleven more for membrane fusion and core entry. The entry-fusion proteins are conserved in all poxviruses and form a complex, known as the Entry Fusion Complex (EFC), which is embedded in the membrane of the mature virion. An additional membrane that encloses the mature virion and is discarded prior to entry is present on an extracellular form of the virus. The EFC is held together by multiple interactions that depend on nine of the eleven proteins. The entry process can be divided into attachment, hemifusion and core entry. All eleven EFC proteins are required for core entry and at least eight for hemifusion. To mediate fusion the virus particle is activated by low pH, which removes one or more fusion repressors that interact with EFC components. Additional EFC-interacting fusion repressors insert into cell membranes and prevent secondary infection. The absence of detailed structural information, except for two attachment proteins and one EFC protein, is delaying efforts to determine the fusion mechanism.
Topics: Animals; Cell Fusion; Humans; Membrane Fusion; Models, Biological; Poxviridae; Viral Proteins; Virus Internalization
PubMed: 27423915
DOI: 10.1016/j.semcdb.2016.07.015 -
Journal of Neurochemistry Apr 2021The revolution in genetic technology has ushered in a new age for our understanding of the underlying causes of neurodevelopmental, neuromuscular and neurodegenerative... (Review)
Review
The revolution in genetic technology has ushered in a new age for our understanding of the underlying causes of neurodevelopmental, neuromuscular and neurodegenerative disorders, revealing that the presynaptic machinery governing synaptic vesicle fusion is compromised in many of these neurological disorders. This builds upon decades of research showing that disturbance to neurotransmitter release via toxins can cause acute neurological dysfunction. In this review, we focus on disorders of synaptic vesicle fusion caused either by toxic insult to the presynapse or alterations to genes encoding the key proteins that control and regulate fusion: the SNARE proteins (synaptobrevin, syntaxin-1 and SNAP-25), Munc18, Munc13, synaptotagmin, complexin, CSPα, α-synuclein, PRRT2 and tomosyn. We discuss the roles of these proteins and the cellular and molecular mechanisms underpinning neurological deficits in these disorders.
Topics: Animals; Exocytosis; Humans; Membrane Fusion; Neurons; Synaptic Transmission; Synaptic Vesicles; Synaptotagmins
PubMed: 32916768
DOI: 10.1111/jnc.15181 -
Nature Reviews. Microbiology Jul 2015Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This 'one bug-one drug' approach to antiviral drug... (Review)
Review
Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This 'one bug-one drug' approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry.
Topics: Animals; Antiviral Agents; Cell Membrane; Humans; Membrane Fusion; Virus Diseases; Virus Internalization
PubMed: 26075364
DOI: 10.1038/nrmicro3475 -
Current Biology : CB Apr 2018Cells are largely compartmentalized into numerous interacting organelles with dedicated functions in lipid metabolism, energy generation, or protein turnover. In the... (Review)
Review
Cells are largely compartmentalized into numerous interacting organelles with dedicated functions in lipid metabolism, energy generation, or protein turnover. In the past, each organelle has been considered as an isolated unit with an individual proteome, membrane composition, and shape. However, this view is changing rapidly as organelles communicate via contact sites, fuse directly with each other, or correspond via vesicular carriers. Each of these processes disturbs the initial individual character of each organelle and they thus need to be tightly controlled and regulated.
Topics: Animals; Humans; Intracellular Membranes; Lipid Metabolism; Membrane Fusion; Organelles; Protein Subunits; Protein Transport
PubMed: 29689226
DOI: 10.1016/j.cub.2017.12.012 -
Current Opinion in Structural Biology Aug 2015
Topics: Cell Membrane; Membrane Fusion; Membrane Lipids; Membrane Proteins; Periodicals as Topic
PubMed: 26489903
DOI: 10.1016/j.sbi.2015.09.006 -
Molecular Biology of the Cell Mar 2017Recent studies suggest revisions to the SNARE paradigm of membrane fusion. Membrane tethers and/or SNAREs recruit proteins of the Sec 1/Munc18 family to catalyze SNARE... (Review)
Review
Recent studies suggest revisions to the SNARE paradigm of membrane fusion. Membrane tethers and/or SNAREs recruit proteins of the Sec 1/Munc18 family to catalyze SNARE assembly into -complexes. SNARE-domain zippering draws the bilayers into immediate apposition and provides a platform to position fusion triggers such as Sec 17/α-SNAP and/or synaptotagmin, which insert their apolar "wedge" domains into the bilayers, initiating the lipid rearrangements of fusion.
Topics: Animals; Humans; Lipids; Membrane Fusion; Membrane Proteins; Munc18 Proteins; Protein Binding; SNARE Proteins; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
PubMed: 28292915
DOI: 10.1091/mbc.E16-07-0517 -
TheScientificWorldJournal Mar 2010
Topics: Biophysics; Membrane Fusion; Virus Assembly; Virus Physiological Phenomena
PubMed: 20305984
DOI: 10.1100/tsw.2010.53 -
Biochimica Et Biophysica Acta Aug 2003Regulated exocytosis was the first intracellular membrane fusion step that was suggested to involve both Ca(2+) and calmodulin. In recent years, it has become clear that... (Review)
Review
Regulated exocytosis was the first intracellular membrane fusion step that was suggested to involve both Ca(2+) and calmodulin. In recent years, it has become clear that calmodulin is not an essential Ca(2+) sensor for exocytosis but that it is likely to have a more regulatory role. A requirement for cytosolic Ca(2+) in other vesicle fusion events within cells has become apparent and in certain cases, such as homotypic fusion of early endosomes and yeast vacuoles, calmodulin may be the primary Ca(2+) sensor. A number of distinct targets for calmodulin have been identified including SNARE proteins and subunits of the vacuolar ATPase. The extent to which calmodulin regulates different intracellular fusion events through conserved SNARE-dependent or other mechanisms remains to be resolved.
Topics: Animals; Calcium; Calmodulin; Cell Membrane; Exocytosis; Humans; Membrane Fusion; Yeasts
PubMed: 12914954
DOI: 10.1016/s0167-4889(03)00089-2