Characterisation of the active/de-active transition of mitochondrial complex I
| Autor: | Amanda Birch, Alexander Galkin, Marion Babot, Paola Labarbuta |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Protein Conformation
Protein subunit Biophysics Respiratory chain I/R ischemia/reperfusion SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis Mitochondrial complex I Review Mitochondrion Biochemistry DTNB 5 5′-dithiobis-(2-nitrobenzoic acid) NDUFA9 A/D active/de-active transition RNS reactive nitrogen species 03 medical and health sciences 0302 clinical medicine Quinone binding ROS reactive oxygen species Animals Humans DIGE difference gel electrophoresis EEDQ N-ethoxycarbonyl-2-ethoxy-1 2-dihydroquinoline hrCN-PAGE high resolution clear native polyacrylamide gel electrophoresis 030304 developmental biology 0303 health sciences HAR hexaammineruthenium NO nitric oxide Electron Transport Complex I Chemistry SMP submitochondrial particles BN-PAGE blue native polyacrylamide gel electrophoresis SPDP N-succinimidyl 3-(2-pyridyldithio)-propionate Thiol modification Cell Biology Ischaemia/reperfusion Conformational change NHS N-hydroxysuccinimide NADH dihydronicotinamide adenine dinucleotide Q ubiquinone Mitochondrial respiratory chain GSH/GSSG reduced/oxidised glutathione Mitochondrial matrix Reperfusion Injury NEM N-ethylmaleimide EMCS N-ε-maleimidocaproyl-oxysuccinimide ester A/D transition 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta Babot, M, Birch, A, Labarbuta, P & Galkin, A 2014, ' Characterisation of the active/de-active transition of mitochondrial complex I ', Biochimica et Biophysica Acta-Bioenergetics, vol. 1837, no. 7, pp. 1083–1092 . https://doi.org/10.1016/j.bbabio.2014.02.018 |
| ISSN: | 0006-3002 |
| DOI: | 10.1016/j.bbabio.2014.02.018 |
| Popis: | Oxidation of NADH in the mitochondrial matrix of aerobic cells is catalysed by mitochondrial complex I. The regulation of this mitochondrial enzyme is not completely understood. An interesting characteristic of complex I from some organisms is the ability to adopt two distinct states: the so-called catalytically active (A) and the de-active, dormant state (D). The A-form in situ can undergo de-activation when the activity of the respiratory chain is limited (i.e. in the absence of oxygen). The mechanisms and driving force behind the A/D transition of the enzyme are currently unknown, but several subunits are most likely involved in the conformational rearrangements: the accessory subunit 39 kDa (NDUFA9) and the mitochondrially encoded subunits, ND3 and ND1. These three subunits are located in the region of the quinone binding site. The A/D transition could represent an intrinsic mechanism which provides a fast response of the mitochondrial respiratory chain to oxygen deprivation. The physiological role of the accumulation of the D-form in anoxia is most probably to protect mitochondria from ROS generation due to the rapid burst of respiration following reoxygenation. The de-activation rate varies in different tissues and can be modulated by the temperature, the presence of free fatty acids and divalent cations, the NAD+/NADH ratio in the matrix, the presence of nitric oxide and oxygen availability. Cysteine-39 of the ND3 subunit, exposed in the D-form, is susceptible to covalent modification by nitrosothiols, ROS and RNS. The D-form in situ could react with natural effectors in mitochondria or with pharmacological agents. Therefore the modulation of the re-activation rate of complex I could be a way to ameliorate the ischaemia/reperfusion damage. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Guest Editors: Manuela Pereira and Miguel Teixeira. Graphical abstract Highlights • The potential mechanism of complex I A/D transition is discussed. • An —SH group exposed in the D-form is susceptible to covalent modification. • The role of A/D transition in tissue response to ischaemia is proposed. |
| Databáze: | OpenAIRE |
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