Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Comparison of SkQ1 and C₁₂TPP effects on the uncoupling activity of DNP and FCCP.

<p>Effects of 2 µM SkQ1, 2 µM C₁₂TPP or 200 µM TPP on the dependence of mitochondrial membrane potential on the concentration of DNP (panel A) or FCCP (panel B). The experiments were conducted in a way shown in Fig. 6. Shown are Mean±S.E. of 4–6 experiments.</p

C₁₂TPP enhances protonophorous effect of 2 nM FCCP (panel A) and 10 µM DNP (panel B) in bilayer lipid membrane (BLM).

<p>Diffusion potential was recorded upon the addition of KOH in one compartment to create ΔpH = 1. Incubation mixture, 10 mM Tris, 10 mM MES, 10 mM KCl, pH 7; C₁₂TPP, 0.1 µM. Control, a record without C₁₂TPP and uncouplers. Plus sign of the potential in the compartment of high pH.</p

CCCP increases the SkQ-induced efflux of carboxyfluorescein from liposomes.

<p>Carboxyfluorescein (CF) efflux from DPhPC (diphytanoylphosphatidylcholine) liposomes (50 µg/ml), induced by 2.5 µM SkQ1 (panel A) or by 0.5 µM SkQR1 (panel B) was measured with or without CCCP. The efflux was accompanied by an increase in CF fluorescence due to dilution and a relief of CF self-quenching. In panel B, the CF efflux was measured 400 s after the addition of SkQR1. Incubation mixture, 10 mM Tris, 10 mM MES, 100 mM KCl, pH 7.</p

SkQ1 (10-(6-plastoquinonyl)decyl triphenylphosphonium) affects absorption spectra of CCCP in the presence of liposomes.

<p>Incubation mixture: 4 µM CCCP, 1 mM Tris, 1 mM MES, pH = 7.4, containing DPhPC (diphytanoylphosphatidylcholine) liposomes (20 µg/ml) in the absence (curve 1) and in the presence of 1 µM, 2 µM, 4 µM and 9 µM SkQ1 (panel A, curves 2–5, respectively) or in the presence of 1 µM, 2 µM, 4 µM and 9 µM SkQR4 (panel B, curves 2–5, respectively). Insert to panel B shows the dependence of λ_max on the concentration of the SkQ derivatives.</p

Chemical structures of C₁₂TPP, SkQ1, SkQR4, C₁₂R4, FCCP, CCCP, DNP, and carboxyfluorescein.

<p>Chemical structures of C₁₂TPP, SkQ1, SkQR4, C₁₂R4, FCCP, CCCP, DNP, and carboxyfluorescein.</p

C₁₂TPP enlarges the FCCP- and DNP-induced increase in respiration rates of intact yeast cells.

<p>The ordinate represents the ratio of the oxygen consumption rates after (V) and before (V₀) the addition of an uncoupler. (A) FCCP-mediated stimulation of yeast respiration in the absence (solid line) and in the presence (dotted line) of 1 µM C₁₂TPP. (B) DNP stimulation of yeast respiration in the absence (solid line) and in the presence of 0.5 µM (dotted line) or 1 µM (dot and dash line) C₁₂TPP. In the absence of the anionic uncoupler, C₁₂TPP did not increase the rate of oxygen consumption at concentrations below 2 µM (insert). Shown are Mean±S.E. of 4 experiments.</p