The protonmotive force and respiratory control

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COST Action CA15203 (2016-2021): MitoEAGLE
Evolution-Age-Gender-Lifestyle-Environment: mitochondrial fitness mapping

The protonmotive force and respiratory control

OXPHOS-coupled energy cycles. From Gnaiger 2014 MitoPathways.

» WG1 Action - WG1 MITOEAGLE protocols, terminology, documentation: Standard operating procedures and user requirement document: Protocols, terminology, documentation

» WG1 Project application

Capacities of the electron transfer system, oxidative phosphorylation and resting LEAK respiration (ETS, OXPHOS, LEAK) and four-compartmental OXPHOS model. (i) Capacity of the ETS module, E, in the noncoupled state, generating the protonmotive force, Δp_mt. OXPHOS capacity, P, is partitioned into (ii) the dissipative LEAK component, L (disspation of Δp_mt), and (iii) the free OXPHOS capacity, ≈P=P-L (energy conversion driven by Δp_mt). If ≈P is limited by the capacity of the phosphorylation system, then (iv) the apparent ETS excess capacity, ExP=E-P, is available to drive coupled processes other than phosphorylation without competing with ATP production. Free divided by total ETS capacity, ≈E/E, is the ETS coupling efficiency. Free divided by total OXPHOS capacity, ≈P/P, is the OXPHOS coupling efficiency. From Gnaiger 2014 MitoPathways.

Mitochondrial respiratory coupling control - a conceptual perspective on terminology

Scope of MITOEAGLE publication: Respiratory states

Target a broad audience – also the new generation
List of terms including historical terms; abbreviations (mtDNA, mt to abbreviate mitochondr*); OXPHOS capacity versus State 3 (discuss saturating ADP/Pi .. concentrations)
Scientific terminology should be general and platform independent - demands of the working groups

Structure

From bioenergetics to mitochondrial physiology - historical view
The mitochondrial respiratory system
Rates and states - Units (important for a database); analogous to electic terms: Flow [C.s-1]; Flux [C.s-1.m-2]; Rate (?)
Intact cells, mt preparation and normalization
Coupling states: mt-preparations and intact cells
Pathway states: mt-preparations and intact cells
References

Journal

Int J Biochem Cell Biol (W Koopman will be the new editor); Open Access is a requirement

Abstract

Prepared by Gnaiger E 2017-04-12

Clarity of concepts and consistency of nomenclature is a signature of the quality of a research area across its specializations, aimed at facilitating translational communication and teaching. The expanding field of mitochondrial respiratory physiology will benefit from a harmonization of nomenclature on mitochondrial respiratory states and control parameters. Development of databases on mitochondrial respiratory control requires application of strictly defined terms for all included variables. Peter Mitchell’s protonmotive, chemiosmotic force across the inner mitochondrial membrane, Δp_mt, establishes the link between electron transfer and phosphorylation of ADP to ATP, and between the chemical (pH difference, ΔpH) and electric (mt-membrane potential difference, ΔΨ_mt) components of energy transformation. This unifying concept provides the general framework upon which a consistent terminology on mitochondrial physiology and bioenergetics can be based. IUPAC guidelines are followed for general terms of physical chemistry, extended by concepts of nonequilibrium thermodynamics and open systems. The differential nomenclature of classical bioenergetics (numerical differentiation of experimental protocol-linked respiratory States 1, 2, 3, 4 and 5) is incorporated into a concept-driven constructive terminology to address the basic meaning of a respiratory state and direct attention from the experimental ‘how’ to the concentual ‘why’. LEAK states are evaluated to study resting respiration, L, compensating mainly for the proton leak. OXPHOS capacity, P, is measured at saturating levels of ADP and inorganic phosphate to obtain kinetic references values for diagnostic applications. The ETS state differentiates the oxidative capacity of the electron transfer system, E, from OXPHOS capacity, revealing a limitation of P by the phosphorylation system.

References

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Estabrook R (1967) Mitochondrial respiratory control and the polarographic measurement of ADP:O ratios. Meth Enzymol 10:41-7. - »Bioblast link«
Gnaiger E (1993) Nonequilibrium thermodynamics of energy transformations. Pure Appl Chem 65:1983-2002. - »Bioblast link«
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Gnaiger 2014 MitoPathways
International Union of Biochemistry and Molecular Biology: Recommendations for terminology and databases for biochemical thermodynamics. - »Open Access«
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Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144-8. - »Bioblast link«

Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Glynn Research Ltd, Bodmin:192 pp. - The Grey Book 1.
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Action

» Pre-publication: Mitochondrial respiratory control states

» MitoPedia: Respiratory control ratios

» MitoPedia: SUIT

» 2017-07 MiPschool Obergurgl 2017

» 2017-03 MITOEAGLE Barcelona 2017

» 2016-11 MITOEAGLE 2016 Verona IT

Next steps

Mitochondrial respiratory pathway control - substrates and inhibitors

Switch to pathway-related nomenclature instead of enzyme-linked terminology (N/NS/S versus CI/CI+II/CII)