Yin 2021 FASEB J

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Publications in the MiPMap
Yin M, O'Neill LAJ (2021) The role of the electron transport chain in immunity. FASEB J 35:e21974. https://doi.org/10.1096/fj.202101161R

Β» PMID: 34793601 Open Access

Yin M, O'Neill LAJ (2021) FASEB J

Abstract: The electron transport chain (ETC) couples oxidative phosphorylation (OXPHOS) with ATP synthase to drive the generation of ATP. In immune cells, research surrounding the ETC has drifted away from bioenergetics since the discovery of cytochrome c (Cyt c) release as a signal for programmed cell death. Complex I has been shown to generate reactive oxygen species (ROS), with key roles identified in inflammatory macrophages and T helper 17 cells (TH 17) cells. Complex II is the site of reverse electron transport (RET) in inflammatory macrophages and is also responsible for regulating fumarate levels linking to epigenetic changes. Complex III also produces ROS which activate hypoxia-inducible factor 1-alpha (HIF-1Ξ±) and can participate in regulatory T cell (Treg ) function. Complex IV is required for T cell activation and differentiation and the proper development of Treg subsets. Complex V is required for TH 17 differentiation and can be expressed on the surface of tumor cells where it is recognized by anti-tumor T and NK cells. In this review, we summarize these findings and speculate on the therapeutic potential of targeting the ETC as an anti-inflammatory strategy.


Correction: FADH2 and Complex II

Ambiguity alert.png
FADH2 is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).
Gnaiger E (2024) Complex II ambiguities ― FADH2 in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470 - Β»Bioblast linkΒ«

Hydrogen ion ambiguities in the electron transfer system

Communicated by Gnaiger E (2023-10-08) last update 2023-11-10
Electron (e-) transfer linked to hydrogen ion (hydron; H+) transfer is a fundamental concept in the field of bioenergetics, critical for understanding redox-coupled energy transformations.
Ambiguity alert H+.png
However, the current literature contains inconsistencies regarding H+ formation on the negative side of bioenergetic membranes, such as the matrix side of the mitochondrial inner membrane, when NADH is oxidized during oxidative phosphorylation (OXPHOS). Ambiguities arise when examining the oxidation of NADH by respiratory Complex I or succinate by Complex II.
Ambiguity alert e-.png
Oxidation of NADH or succinate involves a two-electron transfer of 2{H++e-} to FMN or FAD, respectively. Figures indicating a single electron e- transferred from NADH or succinate lack accuracy.
Ambiguity alert NAD.png
The oxidized NAD+ is distinguished from NAD indicating nicotinamide adenine dinucleotide independent of oxidation state.
NADH + H+ β†’ NAD+ +2{H++e-} is the oxidation half-reaction in this H+-linked electron transfer represented as 2{H++e-} (Gnaiger 2023). Putative H+ formation shown as NADH β†’ NAD+ + H+ conflicts with chemiosmotic coupling stoichiometries between H+ translocation across the coupling membrane and electron transfer to oxygen. Ensuring clarity in this complex field is imperative to tackle the apparent ambiguity crisis and prevent confusion, particularly in light of the increasing number of interdisciplinary publications on bioenergetics concerning diagnostic and clinical applications of OXPHOS analysis.
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