Conditions allowing redox-cycling ubisemiquinone in mitochondria to establish a direct redox couple with molecular oxygen

Nohl, Hans; Gille, Lars; Schönheit, Katrin; Liu, Yang

doi:10.1016/0891-5849(95)02038-1

Cited by 99 publications

(38 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(•, p < 0.01; *, p < 0.05). (Nohl et al, 1996). Additionally, our experiments indicate that the autoxidation of Q 6 H 2 in the absence of added oxidant, either Cu 2+ or azo initiator, is very minimal since the rate of fluorescence decay is considerably slower in liposomes containing Q 6 H 2 than the rate of oxidation in similar QH 2 / PC liposome systems described by other investigators (Frei et al, 1990), indicating that Q 6 H 2 is more stable in our liposome preparation.…”

Section: Discussionmentioning

confidence: 49%

Autoxidation of Ubiquinol-6 Is Independent of Superoxide Dismutase

et al. 1996

View full text Add to dashboard Cite

Ubiquinone (Q) is an essential, lipid soluble, redox component of the mitochondrial respiratory chain. Much evidence suggests that ubiquinol (QH 2 ) functions as an effective antioxidant in a number of membrane and biological systems by preventing peroxidative damage to lipids. It has been proposed that superoxide dismutase (SOD) may protect QH 2 from autoxidation by acting either directly as a superoxide-semiquinone oxidoreductase or indirectly by scavenging superoxide. In this study, such an interaction between QH 2 and SOD was tested by monitoring the fluorescence of cis-parinaric acid (cPN) incorporated phosphatidylcholine (PC) liposomes. Q 6 H 2 was found to prevent both fluorescence decay and generation of lipid peroxides (LOOH) when peroxidation was initiated by the lipid-soluble azo initiator DAMP, dimethyl 2,2′-azobis (2-methylpropionate), while Q 6 or SOD alone had no inhibitory effect. Addition of either SOD or catalase to Q 6 H 2 -containing liposomes had little effect on the rate of peroxidation even when incubated in 100% O 2 . Hence, the autoxidation of QH 2 is a competing reaction that reduces the effectiveness of QH 2 as an antioxidant and was not slowed by either SOD or catalase. The in ViVo interaction of SOD and QH 2 was also tested by employing yeast mutant strains harboring deletions in either CuZnSOD and/or MnSOD. The sod mutant yeast strains contained the same percent Q 6 H 2 per cell as wild-type cells. These results indicate that the autoxidation of QH 2 is independent of SOD.

show abstract

Section: Discussionmentioning

confidence: 49%

Autoxidation of Ubiquinol-6 Is Independent of Superoxide Dismutase

et al. 1996

View full text Add to dashboard Cite

show abstract

“…11). For a number of reasons, SQ at center o was assumed as the most plausible candidate for univalent oxygen reduction: CoQ may be transformed by a safe electron carrier to a superoxide generator when protons are allowed to penetrate the inner membrane, as in toluene-treated mitochondria (12). Although SQ is autooxidizable in liposomes under suitable conditions (13), no direct demonstration is available for the Figure 1.…”

Section: Complex IIImentioning

confidence: 99%

The Mitochondrial Production of Reactive Oxygen Species: Mechanisms and Implications in Human Pathology

2001

View full text Add to dashboard Cite

SummaryMitochondria are major sources of reactive oxygen species (ROS); the main sites of superoxide radical production in the respiratory chain are Complexes III and I; however, other mitochondrial enzymes, such as Complex II, glycerol-1-phosphate dehydrogenase, and dihydroorotate dehydrogenase, are also involved in production of ROS. ROS appear to be released both in the matrix and in the intermembrane space; however, their appearance outside the mitochondria may not be physiologically relevant. ROS production is increased in State 4 and in all conditions when the respiratory components are substantially in the reduced form. Accordingly, defects inducing decrease of electron transfer in the respiratory chain, as in many pathological conditions, are bound to enhance ROS production.

show abstract

“…Although theoretical arguments have been made about why O~ production (under normal conditions) at Complex III could not occur in vivo (90)(91)(92)(93), experimental evidence clearly suggests that it does (49,67).…”

Section: Thermodynamics Of O~ Formation and Biochemical Characteristimentioning

confidence: 99%

The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Muller

2000

AGE

123

View full text Add to dashboard Cite

Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/ transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity. This paper aims to summarize what is known about the nature and mechanisms of superoxide production and what genes are involved in controlling the rate of superoxide production.

show abstract

Conditions allowing redox-cycling ubisemiquinone in mitochondria to establish a direct redox couple with molecular oxygen

Cited by 99 publications

References 18 publications

Autoxidation of Ubiquinol-6 Is Independent of Superoxide Dismutase

Autoxidation of Ubiquinol-6 Is Independent of Superoxide Dismutase

The Mitochondrial Production of Reactive Oxygen Species: Mechanisms and Implications in Human Pathology

The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Contact Info

Product

Resources

About