Diabetic complications are the leading cause of morbidity and mortality in diabetic patients. Elevated blood glucose contributes to the development of endothelial and vascular dysfunction, and, consequently, to diabetic micro- and macrovascular complications, because it increases the mitochondrial proton gradient and mitochondrial oxidant production. Therapeutic approaches designed to counterac...

Uncoupling protein 1 (UCP1) from mouse was expressed in yeast and the specific (GDP-inhibitable) and artifactual (GDP-insensitive) effects on mitochondrial uncoupling were assessed. UCP1 provides a GDP-inhibitable model system to help interpret the uncoupling effects of high expression in yeast of other members of the mitochondrial carrier protein family, such as the UCP1 homologues UCP2 and UC...

Most of the adenosine triphosphate (ATP) synthesized during glucose metabolism is produced in the mitochondria through oxidative phosphorylation. This is a complex reaction powered by the proton gradient across the mitochondrial inner membrane, which is generated by mitochondrial respiration. A detailed model of this reaction, which includes dynamic equations for the key mitochondrial variables...

Mitochondrial carriers link biochemical pathways in the cytosol and mitochondrial matrix by transporting substrates across the inner mitochondrial membrane. Substrate recognition is specific for each carrier, but sequence similarities suggest the carriers have similar structures and mechanisms of substrate translocation. By considering conservation of amino acids, distance and chemical constrai...

Methylmercury (MeHg) mediated cytotoxicity is associated with loss of intracellular calcium (Ca²⁺) homeostasis. The imbalance in Ca²⁺ physiology is believed to be associated with dysregulation of Ca²⁺ intracellular stores and/or increased permeability of the biomembranes to this ion. In this paper we summarize the contribution of glutamate dyshomeostasis in intracellular Ca²⁺ overload and highl...

It is clearly emerging from the work of various laboratories that membrane-bound electron transfer chains are anisotropically arranged along an axis perpendicular to the plane of the membrane (1-6). Anisotropic organization of redox chains, composed of hydrogen and electron carriers can lead, as proposed by Lundegardh (7), to generation of transmembrane electrical fields and proton gradients if...

Studying differential cell function or dysfunction within the kidney is made difficult by cellular heterogeneity, alterations in regional blood flow, oxygen tension, and interstitial tonicity, resulting in extremely complex anatomic and physiologic arrangements. Creative investigators have developed techniques to reduce this heterogeneity but often with loss or alteration of three-dimensional c...