The principal mitochondrial K+ uniport is associated with respiratory complex I

Mitochondria generate ATP via coupling the negative electrochemical potential (proton motive force, Capital Greek (Deltap), consisting of a proton gradient (Capital Greek DeltapH+) and a membrane potential (Capital Greek Psim) across the respiratory chain, to phosphorylation of adenosine diphosphate nucleotide. In turn, DeltapH+ and Capital Greek Psim, are tightly balanced by the modulation of ionic uniporters and exchange-diffusion systems which preserve integrity of mitochondrial membranes and regulate ATP production. Here, we provide direct electrophysiological, pharmacological and genetic evidence that the main mitochondrial electrophoretic pathway for monovalent cations is associated with respiratory complex I, contrary to the long-held dogma that only H+ gradients are built across proteins of the mammalian electron transport chain. Here we propose a theoretical framework to describe how monovalent metal cations contribute to the buildup of H+ gradients and the proton motive force, extending the classical Mitchellian view on chemiosmosis and vectorial metabolism. Keywords: mitochondrial electrogenic transport, chemiosmotic theory, vectorial metabolism, whole-mitochondria electrophysiology.

Foundations of Vectorial Metabolism and Osmochemistry

Chemical transformations, like osmotic translocations, are transport processes when looked at in detail. In chemiosmotic systems, the pathways of specific ligand conduction are spatially orientated through osmoenzymes and porters in which the actions of chemical group, electron and solute transfer occur as vectorial (or higher tensorial order) diffusion processes down gradients of total potential energy that represent real spatially directed fields of force. Thus, it has been possible to describe classical bag-of-enzymes biochemistry as well as membrane biochemistry in terms of transport. But it would not have been possible to explain biological transport in terms of classical transformational biochemistry or chemistry. The recognition of this conceptual asymmetry in favour of transport has seemed to be upsetting to some biochemists and chemists; and they have resisted the shift towards thinking primarily in terms of the vectorial forces and co-linear displacements of ligands in place of their much less informative scalar products that correspond to the conventional scalar energies. Nevertheless, considerable progress has been made in establishing vectorial metabolism and osmochemistry as acceptable biochemical disciplines embracing transport and metabolism, and bioenergetics has been fundamentally transformed as a result.

Biochemical topology: From vectorial metabolism to morphogenesis

In living cells, many biochemical processes are spatially organized: they have a location, and often a direction, in cellular space. In the hands of Peter Mitchell and Jennifer Moyle, the chemiosmotic formulation of this principle proved to be the key to understanding biological energy transduction and related aspects of cellular physiology. For H. E. Huxley and A. F. Huxley, it provided the basis for unravelling the mechanism of muscle contraction; and vectorial biochemistry continues to reverberate through research on cytoplasmic transport, motility and organization. The spatial deployment of biochemical processes serves here as a point of departure for an inquiry into morphogenesis and self-organization during the apical growth of fungal hyphae.

Foundations of vectorial metabolism and osmochemistry

Chemical transformations, like osmotic translocations, are transport processes when looked at in detail. In chemiosmotic systems, the pathways of specific ligand conduction are spatially orientated through osmoenzymes and porters in which the actions of chemical group, electron and solute transfer occur as vectorial (or higher tensorial order) diffusion processes down gradients of total potential energy that represent real spatially-directed fields of force. Thus, it has been possible to describe classical bag-of-enzymes biochemistry as well as membrane biochemistry in terms of transport. But it would not have been possible to explain biological transport in terms of classical transformational biochemistry or chemistry. The recognition of this conceptual asymmetry in favour of transport has seemed to be upsetting to some biochemists and chemists; and they have resisted the shift towards thinking primarily in terms of the vectorial forces and co-linear displacements of ligands in place of their much less informative scalar products that correspond to the conventional scalar energies. Nevertheless, considerable progress has been made in establishing vectorial metabolism and osmochemistry as acceptable biochemical disciplines embracing transport and metabolism, and bioenergetics has been fundamentally transformed as a result.