A5050853442- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Neurobiology and Insect Physiology Research
- RNA and protein synthesis mechanisms
- Metabolism and Genetic Disorders
- Signaling Pathways in Disease
- Protein Kinase Regulation and GTPase Signaling
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- RNA modifications and cancer
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Protist diversity and phylogeny
- Cardiac Ischemia and Reperfusion
- Cell death mechanisms and regulation
- Plant and Biological Electrophysiology Studies
- Cellular transport and secretion
- Fuel Cells and Related Materials
- Photosynthetic Processes and Mechanisms
- Invertebrate Immune Response Mechanisms
- Genetic Neurodegenerative Diseases
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Muscle Physiology and Disorders
- RNA Research and Splicing
Louisiana State University Health Sciences Center New Orleans
2025
U.S. Army Engineer Research and Development Center
2022
Vollum Institute
2012-2021
Oregon Health & Science University
2011-2021
West Virginia University
2020
Neuroscience Institute
2015
University of Udine
2015
University of Kansas
2015
University of Padua
2015
University of Virginia
2010
Here we define the molecular nature of mitochondrial permeability transition pore (PTP), a key effector cell death. The PTP is regulated by matrix cyclophilin D (CyPD), which also binds lateral stalk F O 1 ATP synthase. We show that CyPD oligomycin sensitivity-conferring protein subunit enzyme at same site as synthase inhibitor benzodiazepine 423 (Bz-423), Bz-423 sensitizes to Ca 2+ like itself, and decreasing expression RNAi increases sensitivity . Purified dimers synthase, did not contain...
We have studied the properties of permeability transition pore (PTP) in mitochondria from liver mice where Ppif gene encoding for mitochondrial Cyclophilin D (CyP-D) had been inactivated. Mitochondria Ppif-/- no CyP-D and displayed a striking desensitization PTP to Ca2+, that opening required about twice Ca2+ load necessary open strain-matched, wild-type mitochondria. lacking were insensitive Cyclosporin A (CsA), which increased retention capacity only mice. The response ubiquinone 0,...
Disruptions in mushroom body (MB) or central complex (CC) brain structures impair Drosophila associative olfactory learning. Perturbations adenosine 3′,5′ monophosphate signaling also disrupt To integrate these observations, expression of a constitutively activated stimulatory heterotrimeric guanosine triphosphate-binding protein α subunit (Gα s *) was targeted to structures. The ability associate odors with electroshock abolished when Gα * MB, but not CC, structures, whereas sensorimotor...
Blue native gel electrophoresis purification and immunoprecipitation of F(0)F(1)-ATP synthase from bovine heart mitochondria revealed that cyclophilin (CyP) D associates to the complex. Treatment intact with membrane-permeable bifunctional reagent dimethyl 3,3-dithiobis-propionimidate (DTBP) cross-linked CyPD lateral stalk ATP synthase, whereas no interactions F(1) sector subunits, natural inhibitor protein IF1, ATP/ADP carrier were observed. The synthase-CyPD have functional consequences on...
Type II hexokinase is overexpressed in most neoplastic cells, and it mainly localizes on the outer mitochondrial membrane. Hexokinase dissociation from mitochondria triggers apoptosis. The prevailing model postulates that release its interactor, voltage-dependent anion channel, prompts membrane permeabilization ensuing of apoptogenic proteins, these events are inhibited by growth factor signalling. Here we show a N-terminal peptide selectively detaches activates These abrogated inhibiting...
The gene encoding the yeast mitochondrial outer membrane channel VDAC was subjected to site-directed mutagenesis change amino acids at 29 positions residues differing in charge from wild-type sequence. mutant genes were then expressed yeast, and physiological consequences of single multiple acid changes assessed after isolation insertion channels into phospholipid bilayers. Selectivity observed 14 sites distributed throughout length molecule. These are likely define position protein walls...
The voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane is a small abundant protein found in all eukaryotic kingdoms which forms voltage-gated pore when incorporated into planar lipid bilayers. VDAC also site binding metabolic enzymes hexokinase and glycerol kinase to mitochondrion what may be significant regulatory interaction. Recently, there has been speculation that multiple mammals differ their localization physiological function. In this report, we describe...
Multiple sclerosis (MS) is the leading cause of neurological disability in young adults, affecting some two million people worldwide. Traditionally, MS has been considered a chronic, inflammatory disorder central white matter which ensuing demyelination results physical [Frohman EM, Racke MK, Raine CS (2006) N Engl J Med 354:942-955]. More recently, become increasingly viewed as neurodegenerative neuronal loss, axonal injury, and atrophy CNS lead to permanent clinical disability. Although...
Aerobic energy metabolism in cells involves the transfer of reducing equivalents from organic molecules to oxygen. NADH is important as a carrier these and feedback regulator glycolysis. We report that micromolar quantities double voltage dependence mitochondrial channel, VDAC, critical pathway for flux metabolites between cytoplasm spaces. In presence NADH, opening closing this channel more sensitive changes membrane potential thus presumably better able respond metabolic conditions. This...
The purification and characterization of acetylcholinesterase from heads the fruit fly Drosophila are described. Sequential extraction procedures indicated that approximately 40% activity was soluble 60% membrane-bound virtually none (less than 4%) corresponded to collagen-tailed forms. enzyme extracted with Triton X-100 purified over 4000-fold by affinity chromatography on acridinium resin. Hydrodynamic analysis both sucrose gradient centrifugation Sepharose CL-4B revealed an Mr 165,000...
We report here on the isolation and characterization of a serotonin (5HT) transporter from Drosophila melanogaster. A 3.1-kb complementary DNA clone (dSERT) was found to encode protein 622 amino acid residues with predicted molecular mass approximately 69 kDa putative transmembrane topology characteristic cloned members mammalian Na+/Cl- neurotransmitter cotransporter gene family. dSERT displays highest overall sequence identity 5HT (51%), norepinephrine (47%), dopamine (47%) transporters...
Energized mouse liver mitochondria displayed the same calcium retention capacity (a sensitive measure of propensity permeability transition pore (PTP) to open) irrespective whether phosphate, arsenate, or vanadate was permeating anion. Unexpectedly, however, phosphate specifically required for PTP desensitization by cyclosporin A (CsA) genetic inactivation cyclophilin D (CyP-D). Indeed, when replaced vanadate, bicarbonate, inhibitory effects CsA and CyP-D ablation on disappeared. After...
Purified F-ATP synthase dimers of yeast mitochondria display Ca2+-dependent channel activity with properties resembling those the permeability transition pore (PTP) mammals. After treatment Ca2+ ionophore ETH129, which allows electrophoretic uptake, isolated undergo inner membrane permeabilization due to PTP opening. Yeast mutant strains ΔTIM11 and ΔATP20 (lacking e g subunits, respectively, are necessary for dimer formation) a striking resistance These results show that originates from...