A5032321673- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Photosynthetic Processes and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Microtubule and mitosis dynamics
- Metabolism and Genetic Disorders
- Streptococcal Infections and Treatments
- Cardiomyopathy and Myosin Studies
- Retinal Development and Disorders
- Studies on Chitinases and Chitosanases
- Toxin Mechanisms and Immunotoxins
- Signaling Pathways in Disease
- Metabolomics and Mass Spectrometry Studies
- Antimicrobial Resistance in Staphylococcus
- RNA Interference and Gene Delivery
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- Enzyme Production and Characterization
- Virus-based gene therapy research
- Cellular Mechanics and Interactions
- Heat shock proteins research
Case Western Reserve University
2015-2024
University School
2010-2024
Scripps Research Institute
2005-2011
University of Oklahoma Health Sciences Center
2005
Texas A&M University
2002-2004
Cytosolic dynamin-related protein 1 (Drp1, also known as DNM1L) is required for both mitochondrial and peroxisomal fission. Drp1-dependent division of these organelles facilitated by a number adaptor proteins at surfaces. To investigate the interplay proteins, we used gene-editing technology to create suite cell lines lacking adaptors MiD49 (also MIEF2), MiD51 MIEF1), Mff Fis1. Increased connectivity was observed following loss individual adaptors, this further enhanced combined Mff....
The GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial division, but the mechanisms remain poorly understood. Much of what is attributed to Drp1’s mechanism action in membrane fission parallels that prototypical dynamin endocytic vesicle scission. Unlike case for dynamin, however, no lipid target Drp1 activation at mitochondria has been identified. In addition, oligomerization properties have not well established. We show mitochondria-specific cardiolipin a potent stimulator...
Cardiolipin (CL) is an atypical, dimeric phospholipid essential for mitochondrial dynamics in eukaryotic cells. Dynamin-related protein 1 (Drp1), a cytosolic member of the dynamin superfamily large GTPases, interacts with CL and functions to sustain balance division fusion by catalyzing fission. Although recent studies have indicated role stimulating Drp1 self-assembly GTPase activity at membrane surface, mechanism which fission, if all, remains unclear. Here, using variety fluorescence...
Abstract Mitochondrial fragmentation and bioenergetic failure manifest in Huntington’s disease (HD), a fatal neurodegenerative disease. The factors that couple mitochondrial fusion/fission with bioenergetics their impacts on neurodegeneration however remain poorly understood. Our proteomic analysis identifies protein ATAD3A as an interactor of fission GTPase, Drp1, HD. Here we show that, HD, dimerization due to deacetylation at K135 residue is required for Drp1-mediated fragmentation....
Abstract Mitochondrial fission is a critical cellular event to maintain organelle function. This multistep process initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at surface mitochondria. As such, Drp1 essential for inducing mitochondrial division in mammalian cells, homologous proteins are found all eukaryotes. member dynamin superfamily (DSPs), controlled self-assembly into large helical polymers stimulates its GTPase activity promote membrane...
The GTPase dynamin catalyzes the scission of deeply invaginated clathrin-coated pits at plasma membrane, but mechanisms governing dynamin-mediated membrane fission remain poorly understood. Through mutagenesis, we have altered hydrophobic nature membrane-inserting variable loop 1 (VL1) pleckstrin homology (PH) domain dynamin-1 and demonstrate that its stable insertion into lipid bilayer is critical for high curvature generation subsequent fission. Dynamin PH mutants defective in regain...
Dynamin 1 (Dyn1) and Dyn2 are neuronal ubiquitously expressed isoforms, respectively, of the multidomain GTPase required for clathrin-mediated endocytosis (CME). Although they 79% identical, Dyn1 not fully functionally redundant. Through direct measurements basal assembly-stimulated activities, membrane binding, self-assembly, fission on planar curved templates, we have shown that is an efficient curvature generator, whereas primarily a sensor. Using Dyn1/Dyn2 chimeras, identified...
Significance The large cytosolic GTPase dynamin-related protein 1 (Drp1) self-assembles around mitochondria to mechanoenzymatically constrict and divide the double-membrane–bound organelle. Although Drp1 recruitment mitochondrial surface is contingent upon its binding adaptors, subsequent or coincident interactions with outer membrane–localized, mitochondria-specific phospholipid cardiolipin (CL) critical for stress-induced fission. Here, using a combination of multimodal NMR spectroscopy...
The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at extreme Drp1 C-terminus, named CT-SLiM, constitutes critical allosteric site controls structure function in vitro vivo. Extension of CT-SLiM by non-native residues, or its interaction with partner GIPC-1, constrains subunit conformational dynamics,...
FRET measurements were used to determine the domain-specific topography of perfringolysin O, a pore-forming toxin, on membrane surface at different stages pore formation. The data reveal that elongated toxin monomer binds stably in an “end-on” orientation, with its long axis approximately perpendicular plane bilayer. This orientation is largely retained even after association form oligomeric prepore complex. domain 3 (D3) polypeptide segments ultimately transmembrane β-hairpins remain far...
Green fluorescent protein (GFP)-tagging is the prevalent strategy to monitor dynamics in living cells. However, consequences of appending bulky GFP moiety interest are rarely investigated. Here, using a powerful combination quantitative fluorescence spectroscopic and imaging techniques, we have examined oligomerization GFP-tagged mitochondrial fission GTPase dynamin-related 1 (Drp1) both vitro vivo. We find that Drp1 exhibits impaired equilibria solution corresponds greatly diminished...