A new way of understanding bioenergetics
Abstract
Extra-mitochondrial oxidative phosphorylation that leads to the production of energy,
in the form of ATP, has been shown to occur in the rod outer segments in the retina. This
supplies energy for the process whereby light is converted to an electrical impulse and
carried by the optic nerve to the brain. Professor Alessandro Maria Morelli and Professor
Isabella Panfoli, from the University of Genoa, Italy, show that extra-mitochondrial
oxidative phosphorylation also occurs in the myelin sheath surrounding nerves, and
suggest that it is a vital energy supply for the nerve.
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The existence of different conductive patterns in unmyelinated and myelinated axons is uncertain. It seems that considering exclusively physical electrical phenomena may be an oversimplification. A novel interpretation of the mechanism of nerve conduction in myelinated nerves is proposed, to explain how the basic mechanism of nerve conduction has been adapted to myelinated conditions.
The neurilemma would bear the voltage-gated channels and Na⁺/K⁺-ATPase in both unmyelinated and myelinated conditions, the only difference being the sheath wrapping it. The dramatic increase in conduction speed of the myelinated axons would essentially depend on an increment in ATP availability within the internode: myelin would be an aerobic ATP supplier to the axoplasm, through connexons. In fact, neurons rely on aerobic metabolism and on trophic support from oligodendrocytes, that do not normally duplicate after infancy in humans.
Such comprehensive framework of nerve impulse propagation in axons may shed new light on the pathophysiology of nervous system disease in humans, seemingly strictly dependent on the viability of the pre-existing oligodendrocyte.
The disks of the vertebrate retinal rod Outer Segment (OS), devoid of mitochondria, are the site of visual transduction, a very energy demanding process. In a previous proteomic study we reported the expression of the respiratory chain complexes I-IV and the oxidative phosphorylation Complex V (F(1)F(0)-ATP synthase) in disks. In the present study, the functional localization of these proteins in disks was investigated by biochemical analyses, oxymetry, membrane potential measurements, and confocal laser scanning microscopy. Disk preparations, isolated by Ficoll flotation, were characterized for purity. An oxygen consumption, stimulated by NADH and Succinate and reverted by rotenone, antimycin A and KCN was measured in disks, either in coupled or uncoupled conditions. Rhodamine-123 fluorescence quenching kinetics showed the existence of a proton potential difference across the disk membranes. Citrate synthase activity was assayed and found enriched in disks with respect to ROS. ATP synthesis by disks (0.7 micromol ATP/min/mg), sensitive to the common mitochondrial ATP synthase inhibitors, would largely account for the rod ATP need in the light. Overall, data indicate that an oxidative phosphorylation occurs in rod OS, which do not contain mitochondria, thank to the presence of ectopically located mitochondrial proteins. These findings may provide important new insight into energy production in outer segments via aerobic metabolism and additional information about protein components in OS disk membranes.