Difference between revisions of "Uncoupled respiration"
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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. | ==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 [[uncoupler]]s (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. | |||
Revision as of 08:38, 31 May 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 topics:
Uncoupler
Labels:
Enzyme: Uncoupler Protein"Uncoupler Protein" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Coupling; Membrane Potential"Coupling; Membrane Potential" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
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.
