Did you mean: guanosine triphosphatase
-
Biological Reviews of the Cambridge... May 2018Mitochondria are highly dynamic organelles that constantly migrate, fuse, and divide to regulate their shape, size, number, and bioenergetic function. Mitofusins... (Review)
Review
Mitochondria are highly dynamic organelles that constantly migrate, fuse, and divide to regulate their shape, size, number, and bioenergetic function. Mitofusins (Mfn1/2), optic atrophy 1 (OPA1), and dynamin-related protein 1 (Drp1), are key regulators of mitochondrial fusion and fission. Mutations in these molecules are associated with severe neurodegenerative and non-neurological diseases pointing to the importance of functional mitochondrial dynamics in normal cell physiology. In recent years, significant progress has been made in our understanding of mitochondrial dynamics, which has raised interest in defining the physiological roles of key regulators of fusion and fission and led to the identification of additional functions of Mfn2 in mitochondrial metabolism, cell signalling, and apoptosis. In this review, we summarize the current knowledge of the structural and functional properties of Mfn2 as well as its regulation in different tissues, and also discuss the consequences of aberrant Mfn2 expression.
Topics: GTP Phosphohydrolases; Gene Expression Regulation, Enzymologic; Humans; Mitochondria; Mitochondrial Proteins
PubMed: 29068134
DOI: 10.1111/brv.12378 -
The Journal of Membrane Biology Dec 2022Membrane fusion plays a lead role in the transport of vesicles, neurotransmission, mitochondrial dynamics, and viral infection. There are fusion proteins that catalyze... (Review)
Review
Membrane fusion plays a lead role in the transport of vesicles, neurotransmission, mitochondrial dynamics, and viral infection. There are fusion proteins that catalyze and regulate the fusion. Interestingly, various types of fusion proteins are present in nature and they possess diverse mechanisms of action. We have highlighted the importance of the functional domains of intracellular heterotypic fusion, homotypic endoplasmic reticulum (ER), homotypic mitochondrial, and type-I viral fusion. During intracellular heterotypic fusion, the SNAREs and four-helix bundle formation are prevalent. Type-I viral fusion is controlled by the membrane destabilizing properties of fusion peptide and six-helix bundle formation. The ER/mitochondrial homotypic fusion is controlled by GTPase activity and the membrane destabilization properties of the amphipathic helix(s). Although the mechanism of action of these fusion proteins is diverse, they have some similarities. In all cases, the lipid composition of the membrane greatly affects membrane fusion. Next, examples of lipidation of the fusion proteins were discussed. We suggest that the fatty acyl hydrophobic tail not only acts as an anchor but may also modulate the energetics of membrane fusion intermediates. Lipidation is also important to design more effective peptide-based fusion inhibitors. Together, we have shown that membrane lipid composition and lipidation are important to modulate membrane fusion.
Topics: Membrane Fusion; GTP Phosphohydrolases; Endoplasmic Reticulum; Mitochondrial Dynamics; Lipids
PubMed: 36102950
DOI: 10.1007/s00232-022-00267-5 -
Journal of Molecular and Cellular... May 2020Mitochondria have their own genomes and their own agendas. Like their primitive bacterial ancestors, mitochondria interact with their environment and organelle... (Review)
Review
Mitochondria have their own genomes and their own agendas. Like their primitive bacterial ancestors, mitochondria interact with their environment and organelle colleagues at their physical interfaces, the outer mitochondrial membrane. Among outer membrane proteins, mitofusins (MFN) are increasingly recognized for their roles as arbiters of mitochondria-mitochondria and mitochondria-reticular interactions. This review examines the roles of MFN1 and MFN2 in the heart and other organs as proteins that tether mitochondria to each other or to other organelles, and as mitochondrial anchoring proteins for various macromolecular complexes. The consequences of MFN-mediated tethering and anchoring on mitochondrial fusion, motility, mitophagy, and mitochondria-ER calcium cross-talk are reviewed. Pathophysiological implications are explored from the perspective of mitofusin common functioning as tethering and anchoring proteins, rather than as mediators of individual processes. Finally, some informed speculation is provided for why mouse MFN knockout studies show severe multi-system phenotypes whereas rare human diseases linked to MFN mutations are limited in scope.
Topics: Animals; Biological Transport; GTP Phosphohydrolases; Humans; Mitochondria; Mitochondrial Dynamics; Mitochondrial Membrane Transport Proteins; Protein Multimerization; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 32304672
DOI: 10.1016/j.yjmcc.2020.04.016 -
Current Biology : CB Apr 2018The dynamin superfamily comprises a growing assortment of multi-domain GTPases, found from bacteria to man, that are distinguished from typical GTPases of the Ras, Rab... (Review)
Review
The dynamin superfamily comprises a growing assortment of multi-domain GTPases, found from bacteria to man, that are distinguished from typical GTPases of the Ras, Rab and G-protein families by their modular structure (Figure 1), relatively large size (>70 kDa), and low affinity for guanine nucleotides. In addition, they display a conserved propensity to self-assemble into polymeric arrays, the dynamics of which are regulated by an autonomous, assembly-stimulated GTPase activity.
Topics: Amino Acid Motifs; Conserved Sequence; Dynamins; GTP Phosphohydrolases; Guanosine Triphosphate
PubMed: 29689225
DOI: 10.1016/j.cub.2017.12.013 -
Current Biology : CB Feb 2003
Topics: GTP Phosphohydrolases; GTP-Binding Proteins; Protein Binding; Protein Conformation
PubMed: 12593809
DOI: 10.1016/s0960-9822(03)00069-1 -
Cells Dec 2022GTPases, the molecular switches toggling between an inactive GDP-bound state and an active GTP-bound state, play a pivotal role in controlling complex cellular processes...
GTPases, the molecular switches toggling between an inactive GDP-bound state and an active GTP-bound state, play a pivotal role in controlling complex cellular processes (e [...].
Topics: GTP Phosphohydrolases
PubMed: 36552819
DOI: 10.3390/cells11244055 -
Biochimica Et Biophysica Acta Aug 1998Rab proteins form the largest branch of the Ras superfamily of GTPases. They are localized to the cytoplasmic face of organelles and vesicles involved in the... (Review)
Review
Rab proteins form the largest branch of the Ras superfamily of GTPases. They are localized to the cytoplasmic face of organelles and vesicles involved in the biosynthetic/secretory and endocytic pathways in eukaryotic cells. It is now well established that Rab proteins play an essential role in the processes that underlie the targeting and fusion of transport vesicles with their appropriate acceptor membranes. However, the recent discovery of several putative Rab effectors, which are not related to each other and which fulfil diverse functions, suggests a more complex role for Rab proteins. At least two Rab proteins act at the level of the Golgi apparatus. Rab1 and its yeast counterpart Ypt1 control transport events through early Golgi compartments. Work from our laboratory points out a role for Rab6 in intra-Golgi transport, likely in a retrograde direction.
Topics: Animals; Carrier Proteins; GTP Phosphohydrolases; GTP-Binding Proteins; Golgi Apparatus; Humans; Monomeric GTP-Binding Proteins; Saccharomyces cerevisiae Proteins; rab GTP-Binding Proteins; ras Proteins
PubMed: 9714762
DOI: 10.1016/s0167-4889(98)00050-0 -
Small GTPases Sep 2018The mechanistic target of rapamycin (mTOR) is an evolutionary conserved protein with a serine/threonine kinase activity that regulates cell growth, proliferation,... (Review)
Review
The mechanistic target of rapamycin (mTOR) is an evolutionary conserved protein with a serine/threonine kinase activity that regulates cell growth, proliferation, motility, survival, protein synthesis, autophagy and transcription. It is embedded in 2 large protein complexes: mTORC1 and mTORC2. Regulation of specific mTOR pathway functions depends on multiple GTPases, that act either as regulators of mTOR protein complexes, coupling energy availability with mTORC1 activity, or as downstream effectors of both mTORC1 and mTORC2. In this commentary, we highlight the advantages of studying the mTOR pathway in C. elegans, including the subcellular localization of the signaling pathway components and the animal phenotypes following tissue specific protein over-expression or knockdown. One important regulator that is not limited to the mTOR pathway is RHEB. We discuss in vitro and in vivo data suggesting that RHEB can function as an inhibitor of mTOR when not bound to GTP. RHEB-1 itself is regulated by Rab GDP dissociation inhibitor β, which directly binds to ATX-2. We also highlight the roles of these proteins in dietary restriction-depended reduction in animal size and fat content.
Topics: Animals; Caenorhabditis elegans; GTP Phosphohydrolases; TOR Serine-Threonine Kinases
PubMed: 27854154
DOI: 10.1080/21541248.2016.1247940 -
Molecular Cell Mar 2022A unifying feature of the RAS superfamily is a conserved GTPase cycle by which these proteins transition between active and inactive states. We demonstrate that...
A unifying feature of the RAS superfamily is a conserved GTPase cycle by which these proteins transition between active and inactive states. We demonstrate that autophosphorylation of some GTPases is an intrinsic regulatory mechanism that reduces nucleotide hydrolysis and enhances nucleotide exchange, altering the on/off switch that forms the basis for their signaling functions. Using X-ray crystallography, nuclear magnetic resonance spectroscopy, binding assays, and molecular dynamics on autophosphorylated mutants of H-RAS and K-RAS, we show that phosphoryl transfer from GTP requires dynamic movement of the switch II region and that autophosphorylation promotes nucleotide exchange by opening the active site and extracting the stabilizing Mg. Finally, we demonstrate that autophosphorylated K-RAS exhibits altered effector interactions, including a reduced affinity for RAF proteins in mammalian cells. Thus, autophosphorylation leads to altered active site dynamics and effector interaction properties, creating a pool of GTPases that are functionally distinct from their non-phosphorylated counterparts.
Topics: Animals; Crystallography, X-Ray; GTP Phosphohydrolases; Guanosine Triphosphate; Mammals; Nucleotides; Proteins; Signal Transduction
PubMed: 35202574
DOI: 10.1016/j.molcel.2022.02.011 -
Cell Death & Disease Feb 2018Mitochondria are highly dynamic organelles whose functions are essential for cell viability. Within the cell, the mitochondrial network is continuously remodeled through... (Review)
Review
Mitochondria are highly dynamic organelles whose functions are essential for cell viability. Within the cell, the mitochondrial network is continuously remodeled through the balance between fusion and fission events. Moreover, it dynamically contacts other organelles, particularly the endoplasmic reticulum, with which it enterprises an important functional relationship able to modulate several cellular pathways. Being mitochondria key bioenergetics organelles, they have to be transported to all the specific high-energy demanding sites within the cell and, when damaged, they have to be efficiently removed. Among other proteins, Mitofusin 2 represents a key player in all these mitochondrial activities (fusion, trafficking, turnover, contacts with other organelles), the balance of which results in the appropriate mitochondrial shape, function, and distribution within the cell. Here we review the structural and functional properties of Mitofusin 2, highlighting its crucial role in several cell pathways, as well as in the pathogenesis of neurodegenerative diseases, metabolic disorders, cardiomyopathies, and cancer.
Topics: Animals; Cardiomyopathies; GTP Phosphohydrolases; Humans; Metabolic Diseases; Mitochondrial Proteins; Neoplasms; Neurodegenerative Diseases
PubMed: 29491355
DOI: 10.1038/s41419-017-0023-6