Electrochemical and Thermodynamic Oscillations in the Mitochondrial Life Cycle (Biogenesis): Predictors of Calcium Lithogenesis

Mitochondrial (M) biogenesis (life cycle) consists of repeated changes in its own architectonics, which are conventionally considered in 2 tectonic forms: (1) fusion (integration, or merging into a network tubular composition in which the area of the outer M membrane is minimized, reducing heat transfer and (2) fission (disintegration, or dividing into many small isolated fragments in which the area of the outer M membrane reaches its maximum (10–15 times), increasing heat transfer). In strict correspondence (coherently) with M biogenesis, their functional states change cyclically, accompanied by oscillations of thermodynamic (TD) and electrochemical (EC) potentials. From the viewpoint of non-equilibrium thermodynamics, four functional M states (F states) are considered when applying it to biophysical and biochemical processes where, coherently with a change in the thermal potential (∆Q) in the thickness of the inner M membrane, the speed of electron movement along the respiratory chain changes naturally. A feature of these four functional M states is the possibility of two reverse transitions occurring. Exothermic processes (heat production) predominate in the first transition (F-I \( \rightleftharpoons \) F-IV). Endothermic (heat consumption) predominate in the second (F-II \( \rightleftharpoons \) F-III). At the same time, the long-term predominance of the direction of TD and EC processes with respect to the first reverse transition (F-I \( \rightleftharpoons \) F-IV) is accompanied by chronic exothermic processes caused by uncoupling of the electrochemical potential on the inner M membrane (ΔΨ_m), which under physiological conditions is caused by either fatty acids or thermochemical accumulation in the matrix of Ca²⁺ and Pi cations, in the form of calcium phosphate (CaP) with the release of thermal energy (+4121 kJ/mol). This explains the causal possibility of an exponential (thousandfold) increase in M calcium retention capacity. The imbalance of M biogenesis, with the chronicity of the M functional state in which the first reverse cycle dominates, can be a primordial pathophysiological mechanism of calcigenesis, in which inactive deenergized fragments overflowing with CaP salts undergo mitophagy during M biogenesis, while only the organic substrate undergoes complete autolysis and the remaining inorganic pool is excreted outside the cell in the form of CaP apatite for macrophage use. However, if the local (local) immune response is disturbed by incomplete mitophagy, and/or the lymphatic drainage of the intercellular space is impaired, a pool of CaP accumulates in the interstitial tissues of various organs, contributing to the development of common calcifying diseases (e.g., atherosclerosis, osteochondrosis, and nephrolithiasis).