The eukaryotic porin superfamily consists of two families, voltage-dependent anion channel (VDAC) and Tom40, which are both located in the mitochondrial outer membrane. In Trypanosoma brucei, only a single member of the VDAC family has been described. We report the detection of two additional eukaryotic porin-like sequences in T. brucei. By bioinformatic means, we classify both as putative VDAC...

Voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane, serves as a principal pathway for ATP, ADP, and other respiratory substrates across this membrane. Using umbrella-sampling simulations, we established the thermodynamic and kinetic components governing ATP transport across the VDAC1 channel. We found that there are several low-affinity binding sites f...

Low level lead (Pb) exposure is a risk factor for neurological dysfunction including ADHD. How Pb produces these behavioral deficits is unknown, but low-level exposure during development is associated with auditory temporal processing deficits, even though hearing remains normal. Pb disrupts cellular energy metabolism and efficient energy production is crucial for auditory neurons to maintain t...

Title of dissertation: MITOCHONDRIAL VDAC AND BACTERIAL PORA/C1: ION PERMEATION AND SELECTIVITY Alexander G. Komarov, Doctor of Philosophy, 2005 Dissertation directed by: Professor Marco Colombini Department of Biology VDAC and PorA/C1 are large diameter channels with properties reminiscent of those found in narrow channels. VDAC, located in the mitochondrial outer membrane, shows high selectiv...

A decrease in capillary density due to an increase in endothelial cell apoptosis in the heart is implicated in cardiac ischemia in diabetes. The voltage-dependent anion channel (VDAC) plays a crucial role in the regulation of mitochondrial metabolic function and mitochondria-mediated apoptosis. This study is designed to examine the role of VDAC in coronary endothelial dysfunction in diabetes. E...

Despite a detailed understanding of their metabolism, mitochondria often behave anomalously. In particular, global suppression of mitochondrial metabolism and metabolite exchange occurs in apoptosis, ischemia and anoxia, cytopathic hypoxia of sepsis and multiple organ failure, alcoholic liver disease, aerobic glycolysis in cancer cells (Warburg effect) and unstimulated pancreatic beta cells. He...

The biology and pathogenesis of hepatitis E virus are poorly understood due to the lack of an in vitro culture or infection models. The viral Orf3 protein activates the cellular mitogen-activated protein kinase pathway and is likely to modulate the host cell environment for efficient viral replication. We screened for cellular genes whose transcription was differentially up-regulated in an Orf3...

Insertion of newly synthesized proteins into or across the mitochondrial outer membrane is initiated by import receptors at the surface of the organelle. Typically, this interaction directs the precursor protein into a preprotein translocation pore, comprised of Tom40. Here, we show that a prominent beta-barrel channel protein spanning the outer membrane, human voltage- dependent anion-selectiv...

Value-driven attention capture (VDAC) occurs when previously rewarded stimuli and impair goal-directed behavior. In a working memory (WM) task with VDAC-related distractors, we observe behavioral variability both within across individuals. Individuals differ in their ability to maintain relevant information ignore distractions. These cognitive components shift over time changes motivation atten...

Regulation of mitochondrial outer membrane (MOM) permeability has dual importance: in normal metabolite and energy exchange between mitochondria and cytoplasm and thus in control of respiration, and in apoptosis by release of apoptogenic factors into the cytosol. However, the mechanism of this regulation, dependent on the voltage-dependent anion channel (VDAC), the major channel of MOM, remains...