The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency

Guarás, Adela; Perales‐Clemente, Ester; Calvo, Enrique; Acı́n-Pérez, Rebeca; Loureiro, Marta Bruno; Pujol, Claire; Martínez-Carrascoso, Isabel; Núñez, Estefanía; Garcia-Marques, Fernando Jose; Rodríguez-Hernández, Ángeles; Cortés, Ana; Díaz, Francisca; Pérez‐Martos, Acisclo; Moraes, Carlos T.; Fernández‐Silva, Patricio; Trifunović, Aleksandra; Navas, Plácido; Vázquez, Jesús; Enríquez, José Antonio

doi:10.1016/j.celrep.2016.03.009

Cited by 227 publications

(273 citation statements)

References 53 publications

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“…This leads to disintegration of complex I and reconfiguration of supercomplexes (freeing up complex III), a process that increases electron flux via FADH 2 . All in all, Q redox status acts as a metabolic sensor to adjust the electron transport chain to the high F/N ratio associated with beta oxidation [29]. Mills et al describe the involvement of F/N (QH 2 /Q) ratios in macrophage activation [30].…”

Section: How Do Other Recent Findings Stack Up?mentioning

confidence: 99%

Evolution of peroxisomes illustrates symbiogenesis

Speijer

2017

BioEssays

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Recently, the group of McBride reported a stunning observation regarding peroxisome biogenesis: newly born peroxisomes are hybrids of mitochondrial and ER-derived pre-peroxisomes. What was stunning? Studies performed with the yeast Saccharomyces cerevisiae had convincingly shown that peroxisomes are ER-derived, without indications for mitochondrial involvement. However, the recent finding using fibroblasts dovetails nicely with a mechanism inferred to be driving the eukaryotic invention of peroxisomes: reduction of mitochondrial reactive oxygen species (ROS) generation associated with fatty acid (FA) oxidation. This not only explains the mitochondrial involvement, but also its apparent absence in yeast. The latest results allow a reconstruction of the evolution of the yeast's highly derived metabolism and its limitations as a model organism in this instance. As I review here, peroxisomes are eukaryotic inventions reflecting mutual host endosymbiont adaptations: this is predicted by symbiogenetic theory, which states that the defining eukaryotic characteristics evolved as a result of mutual adaptations of two merging prokaryotes.See also the video abstract here: https://youtu.be/ HtyKhQ3DSxg

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Section: How Do Other Recent Findings Stack Up?mentioning

confidence: 99%

Evolution of peroxisomes illustrates symbiogenesis

Speijer

2017

BioEssays

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“…Recently, succinate-driven RET emerged as a potential area of great physiological importance [18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury

Степанова

Kahl

Konràd

et al. 2017

J Cereb Blood Flow Metab

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Ischemic stroke is one of the most prevalent sources of disability in the world. The major brain tissue damage takes place upon the reperfusion of ischemic tissue. Energy failure due to alterations in mitochondrial metabolism and elevated production of reactive oxygen species (ROS) is one of the main causes of brain ischemia-reperfusion (IR) damage. Ischemia resulted in the accumulation of succinate in tissues, which favors the process of reverse electron transfer (RET) when a fraction of electrons derived from succinate is directed to mitochondrial complex I for the reduction of matrix NAD+. We demonstrate that in intact brain mitochondria oxidizing succinate, complex I became damaged and was not able to contribute to the physiological respiration. This process is associated with a decline in ROS release and a dissociation of the enzyme's flavin. This previously undescribed phenomenon represents the major molecular mechanism of injury in stroke and induction of oxidative stress after reperfusion. We also demonstrate that the origin of ROS during RET is flavin of mitochondrial complex I. Our study highlights a novel target for neuroprotection against IR brain injury and provides a sensitive biochemical marker for this process.

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“…On the other hand, it has been widely demonstrated that organization of these complexes into supra-molecular structures, or supercomplexes, greatly enhances their stability and assembly [5], and also prevents excessive ROS generation [6]. Recent studies showed that the supercomplex association is highly dynamic, and finely tuned by different signaling pathways that are triggered by increased ROS/H 2 O 2 production [7,8], or by mito-energetic dysfunction [9]. This changing organization allows for metabolic compensatory responses that enable mitochondria to promptly sustain the needed levels of cellular ATP.…”

Section: Introductionmentioning

confidence: 99%

Complex II phosphorylation is triggered by unbalanced redox homeostasis in cells lacking complex III

Tropeano

Fiori

Carelli

et al. 2018

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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A marked stimulation of complex II enzymatic activity was detected in cybrids bearing a homoplasmic MTCYB microdeletion causing disruption of both the activity and the assembly of complex III, but not in cybrids harbouring another MTCYB mutation affecting only the complex III activity. Moreover, complex II stimulation was associated with SDHA subunit tyrosine phosphorylation. Despite the lack of detectable hydrogen peroxide production, up-regulation of the levels of mitochondrial antioxidant defenses revealed a significant redox unbalance. This effect was also supported by the finding that treatment with N-acetylcysteine dampened the complex II stimulation, SDHA subunit tyrosine phosphorylation, and levels of antioxidant enzymes. In the absence of complex III, the cellular amount of succinate, but not fumarate, was markedly increased, indicating that enhanced activity of complex II is hampered due to the blockage of respiratory electron flow. Thus, we propose that complex II phosphorylation and stimulation of its activity represent a molecular mechanism triggered by perturbation of mitochondrial redox homeostasis due to severe dysfunction of respiratory complexes. Depending on the site and nature of the damage, complex II stimulation can either bypass the energetic deficit as an efficient compensatory mechanism, or be ineffectual, leaving cells to rely on glycolysis for survival.

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The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency

Cited by 227 publications

References 53 publications

Evolution of peroxisomes illustrates symbiogenesis

Evolution of peroxisomes illustrates symbiogenesis

Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury

Complex II phosphorylation is triggered by unbalanced redox homeostasis in cells lacking complex III

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