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== Abstract continued ==
(ii) In linear pathway states convergent electron entry is blocked and restricted to a single branch of the ETS pathways. Under these conditions of electron gating, control of ET-capacity is exerted mainly by substrate transport into the mitochondria, specific inhibitors applied to block selected mt-pathways, metabolite depletion from the mt-matrix, and activities of mt-matrix dehydrogenases. Electron gating restricts ET-capacity and shifts flux control artificially upstream of the Q-junction. This provides diagnostic information on specific branches of the ETS, particularly with (a) N-linked substrates (PM, GM or PGM; ETC in Fig. 1), (b) S-linked succinate while blocking CI with rotenone, or (c) fatty acid oxidation with a fatty acid (free or bound to carnitine) and malate. Respiratory flux through specific segments of the ETS can be best compared by normalization of flux as substrate control ratios . Electron gating is the basis to evaluate the H+/electron stoichiometry of the proton pumps and the P»/O<sub>2</sub> ratio in the N- versus S-pathway.
Substrate-uncoupler-inhibitor titration (SUIT) protocols are designed to obtain a maximum of diagnostic information in single incubation assays, made possible by multiple sequential titrations in high-resolution respirometry (HRR; Oroboros O2k) . Numerous quantitative studies using SUIT protocols in HRR have become available during the past few years, which reveal a surprising diversity of mitochondrial respiratory control between species, tissues and cell types. This paradigm shift from unity in the biochemistry of bioenergetics to evolutionary diversity of mitochondrial respiratory function sets the foundations of a new comparative mitochondrial physiology . Comprehension of the adaptive traits underlying this functional diversity in pathway control of mitochondrial respiration will be required as a basis to discriminate between mitochondrial health and disease, to develop quantitative mitochondrial fitness scores for specific tissues and cell types, and develop OXPHOS analysis further towards standardized diagnostic tests as required in biomedical studies and clinical applications.
== Figures ==
[[Image:Cape_Town_2015_Gnaiger_Figure.jpg|right|600px]] Figure 1. Electron transfer chain (ETC, linear) versus electron transfer system (ETS, convergent). CI to CIV, Complex I to IV; CGpDH, glycerophosphate dehydrogenase complex; CETF, electron-transferring flavoprotein complex. Electron gating (ETC) limits flux upstream if convergent electron supply exerts an additive effect on ET-capacity. From Gnaiger 2014 .
== Affiliation ==
:::# Swarovski Research Lab, Dept Visceral, Transplant Thoracic Surgery, Medical Univ Innsbruck;
:::# OROBOROS INSTRUMENTS, Innsbruck, Austria. - firstname.lastname@example.org
== References and acknowledgements ==
:::# Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. Oroboros MiPNet Publications, Innsbruck:80 pp.
:::# Hatefi Y, Haavik AG, Fowler LR, Griffiths DE (1962) Studies on the electron transfer-pathway XLII. Reconstitution of the electron transfer-pathway. J Biol Chem 237:2661-9.
:::# Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopsies of human muscle. Meth Mol Biol 810:25-58.
:::# Laner V, Bidaurratzaga E, Gnaiger E, eds (2013) Comparative mitochondrial physiology. MiP2013. Mitochondr Physiol Network 18.08:96 pp.
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