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Difference between revisions of "Uncoupled respiration"

From Bioblast
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{{MitoPedia topics
{{MitoPedia topics
|mitopedia topic=Respiratory state, Uncoupler
|mitopedia topic=Respiratory state, Uncoupler
|type=Respiration
}}
{{Labeling
|discipline=Mitochondrial Physiology
|enzymes=Uncoupler Protein
|topics=Respiration; OXPHOS; ETS Capacity, Coupling; Membrane Potential
|type=Respiration
|type=Respiration
}}
}}

Revision as of 14:44, 17 November 2011


high-resolution terminology - matching measurements at high-resolution


Uncoupled respiration

Description

The uncoupled part of respiration in state P pumps protons to compensate for intrinsic uncoupling, which is a property of (a) the inner mt-membrane (proton leak), (b) the proton pumps (proton slip; decoupling), and (c) is regulated by molecular uncouplers (uncoupling protein, UCP1). Uncoupled and dyscoupled respiration are summarized as LEAK respiration. In contrast, non-coupled respiration is induced experimentally for evaluation of ETS capacity.


Reference: MiPNet12.15, MiPNet10.04


MitoPedia methods: Respirometry 


MitoPedia topics: "Respiratory state" is not in the list (Enzyme, Medium, Inhibitor, Substrate and metabolite, Uncoupler, Sample preparation, Permeabilization agent, EAGLE, MitoGlobal Organizations, MitoGlobal Centres, ...) of allowed values for the "MitoPedia topic" property. Respiratory state"Respiratory state" is not in the list (Enzyme, Medium, Inhibitor, Substrate and metabolite, Uncoupler, Sample preparation, Permeabilization agent, EAGLE, MitoGlobal Organizations, MitoGlobal Centres, ...) of allowed values for the "MitoPedia topic" property., Uncoupler 

Is respiration uncoupled - non-coupled - dyscoupled?

Uncoupled respiration - intrinsic

Uncoupling is used for intrinsic (physiological) uncoupling, appreciating the fact that we do not (never??) find mitochondria to be fully (mechanistically) coupled. In the ROUTINE (intact cells) and OXPHOS (mt-preparations) state of respiration, mitochondria are both, partially coupled and partially uncoupled. The uncoupled part of respiration in state P is larger than LEAK respiration evaluated in state L after inhibition of ATP synthase or adenine nucleotide translocase. This is due to the increase of mt-membrane potential in state L versus P, causing a corresponding increase of the proton leak driven by the higher proton motive force. As an approximation, however, the difference E-L yields an estimate of the physiological scope of uncoupling, or the pathological scope of dyscoupling.

Uncoupled respiration - experimental

Uncoupling is also used for directed experimental interventions to lower the degree of coupling, typically by application of established uncouplers (experimental use of a pharmacological intervention), less typical by freeze-thawing or mechanical crashing of mitochondrial membranes. Such experimental uncoupling can induce stimulation or inhibition of respiration.

Non-coupled respiration

Non-coupled respiration is distinguished from general (pharmacological or mechanical) uncoupled respiration, to give a label to an effort to reach the fully uncoupled (non-coupled) state without inhibiting respiration. Non-coupled respiration, therefore, yields an estimate of ETS capacity. Experimentally uncoupled respiration may fail to yield an estimate of ETS capacity, due to inhibition of respiration above optimum uncoupler concentrations or insufficient stimulation by sub-optimal uncoupler concentrations. Optimum uncoupler concentrations for evaluation of (non-coupled) ETS capacity require inhibitor titrations (Steinlechner-Maran_1996_AJP; Huetter_2004_BJ; Gnaiger_2008_POS).

Dyscoupled respiration

Dyscoupled respiration is distinguished from intrinsically (physiologically) uncoupled and from extrinsic experimentally uncoupled respiration as an indication of extrinsic uncoupling (pathological, toxicological, pharmacological by agents that are not specifically applied to induce uncoupling, but are tested for their potential dyscoupling effect). Dyscoupling indicates a mitochondrial dysfunction.