Biophysical Reviews and Letters

Mitochondrial ATP synthase is a large, membrane-bound protein complex that plays a central role in cellular metabolism. Since the identification of this assembly in micrographs of mitochondrial membranes, electron microscopy has been crucial in elucidating the structure and mechanism of the enzyme. This review addresses the recent use of single particle electron microscopy for structure determination of ATP synthase, including subunit localization, the challenges posed by the protein, and areas in which further work is needed.

It is suggested that the propagation of the action potential is accompanied by an axoplasmic pressure pulse propagating in the axoplasm along the axon length. The pressure pulse stretch-modulates voltage-gated Na⁺ (Nav) channels embedded in the axon membrane, causing their accelerated activation and inactivation and increasing peak channel conductance. As a result, the action potential propagates due to mechano-electrical activation of Nav channels by straggling ionic currents and the axoplasmic pressure pulse. The velocity of such propagation is higher than in the classical purely electrical Nav activation mechanism, and it may be close to the velocity of propagation of pressure pulses in the axoplasm. Extracellular Ca²⁺ ions influxing during the voltage spike, or Ca²⁺ ions released from intracellular stores, may trigger a mechanism that generates and augments the pressure pulse, thus opposing its viscous decay. The model can potentially explain a number of phenomena that are not contained within the purely electrical Hodgkin–Huxley-type framework: the Meyer–Overton rule for the effectiveness of anesthetics, as well as various mechanical, optical and thermodynamic phenomena accompanying the action potential. It is shown that the velocity of propagation of axoplasmic pressure pulses is close to the measured velocity of the nerve impulse, both in absolute magnitude and in dependence on axon diameter, degree of myelination and temperature.

The feedbacks between the mRNA and protein synthesis may result in kinetic bistability and oscillations. Two generic models predicting bistability include, respectively, a gene with positive regulation of the mRNA production by protein and two genes with mutual suppression of the mRNA production due to negative regulation of the gene transcription by protein. The simplest model predicting oscillations describes a gene with negative regulation of the mRNA production by protein formed via mRNA translation and a few steps of conversion. We complement these models by the steps of non-coding RNA (ncRNA) formation and ncRNA-mRNA association and degradation. With this extension, the bistability can often be observed as well. Without and with ncRNA, the biochemistry behind the steady states may be different. In the latter case, for example, ncRNA may control the mRNA population in the situations when this population is relatively small, and one can observe a switch in the mRNA, protein and ncRNA populations. Our analysis of oscillatory kinetics of the mRNA-protein interplay shows that with ncRNA the oscillations may be observed in a wider range of parameters and the amplitude of oscillations may be larger.