Influence of Mitochondrial Radical Formation on Energy‐Linked Respiration

Nohl, Hans; Breuninger, V.; Hegner, D.

doi:10.1111/j.1432-1033.1978.tb12615.x

Cited by 159 publications

(59 citation statements)

References 12 publications

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“…It is reasonable to assume that some of the free radicals generated during the reactions involving oxygen (8,9,13,14), such as the superoxide radical (Ok2), would produce changes in the mitochondria at a rate related to the rate of oxygen consumption. Such alterations (for example, in the mitochondrial DNA) could have an accumulative deleterious effect on mitochondrial functions, leading to the observed mitochondrial changes in number (82,83), morphological characteristics (74), and enzymatic activity (13,(84)(85)(86). Thus, the relationship between life span and basal metabolic rate-to a first approximation, constant throughout life-may reflect the overall rate of accumulation ofmitochondrial damage secondary to free radical reactions (8).…”

Section: )mentioning

confidence: 99%

“…The ubiquitous free radical reactions are initiated continuously throughout cells and tissues from both enzymatic and nonenzymatic reactions; examples include enzymatic reactions involved in the respiratory chain (8,9,13,14), in phagocytosis (10), and in the cytochrome P-450 system (15); nonenzymatic reactions of oxygen (16,17) with organic compounds; and nonenzymatic reactions initiated by ionizing radiation (18). Because of the high chemical reactivity of the intermediates, free radicals, it would be expected that all components ofthe body would be constantly subject to some degree of chemical change in a more-or-less random manner, somewhat like the effects produced by the free radicals formed by ionizing radiation (18).…”

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confidence: 99%

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The aging process.

Harman¹

1981

Proc. Natl. Acad. Sci. U.S.A.

1,575

672

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Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age. These time-related changes are attributed to the aging process. The nature ofthe aging process has been the subject ofconsiderable speculation. Accumulating evidence now indicates that the sum ofthe deleterious free radical reactions going on continuously throughout the cells and tissues constitutes the aging process or is a major contributor to it. In mammalian systems the free radical reactions are largely those involving oxygen.Dietary manipulations expected to lower the rate of production of free radical reaction damage have been shown (i) to increase the life span of mice, rats, fruit flies, nematodes, and rotifers, as well as the "life span" of neurospora; (#-) to inhibit development ofsome forms ofcancer; (ii) to enhance humoral and cell-mediated immune responses; and (iv) to slow development of amyloidosis and the autoimmune disorders of NZB and NZB/NZW mice. In addition, studies strongly suggest that free radical reactions play a significant role in the deterioration of the cardiovascular and central nervous systems with age.The free radical theory of aging provides reasonable explanations for age-associated phenomena, including (i) the relationship of the average life spans of mammalian species to their basal metabolic rates, (ii) the clustering of degenerative diseases in the terminal part of the life span, (iii) the beneficial effect of food restriction on life span, (iv) the greater longevity of females, and (v) the increase in autoimmune manifestations with age.

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Section: )mentioning

confidence: 99%

mentioning

confidence: 99%

The aging process.

Harman¹

1981

Proc. Natl. Acad. Sci. U.S.A.

1,575

672

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“…The endoperoxide pathway has MDA as the end product. phorylation (13,(57)(58)(59). One might speculate that a peculiar membrane lipid composition of these organelles might be responsible for enhanced susceptibility to oxygen radical attack.…”

Section: Mda Release In the Coronary Effluentmentioning

confidence: 99%

Oxygen radicals generated at reflow induce peroxidation of membrane lipids in reperfused hearts.

Ambrosio

Flaherty²,

Duilio³

et al. 1991

J. Clin. Invest.

245

120

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To test whether generation of oxygen radicals during postischemic reperfusion might promote peroxidation of cardiac membrane lipids, four groups of Langendorff-perfused rabbit hearts were processed at the end of (a) control perfusion, (b) 30 min of total global ischemia at 370C without reperfusion, (c) 30 min of ischemia followed by reperfusion with standard perfusate, (d) 30 min of ischemia followed by reperfusion with the oxygen radical scavenger human recombinant superoxide dismutase (h-SOD). The left ventricle was homogenized and tissue content of malonyldialdehyde (MDA), an end product of lipid peroxidation, was measured on the whole homogenate as well as on various subcellular fractions. Reperfusion was accompanied by a significant increase in MDA content of the whole homogenate and of the fraction enriched in mitochondria and lysosomes. This phenomenon was not observed in hearts subjected to ischemia but not reperfused, and was similarly absent in those hearts which received h-SOD at reflow. Reperfused hearts also had significantly greater levels of conjugated dienes (another marker of lipid peroxidation) in the mitochondrial-lysosomal fraction. Again, this phenomenon did not occur in ischemic hearts or in reperfused hearts treated with h-SOD. Unlike the effect on tissue MDA and conjugated dienes, reperfusion did not significantly stimulate release of MDA in the cardiac effluent. Treatment with h-SOD was also associated with significant improvement in the recovery ofcardiac function. In conclusion, these data directly demonstrate that postischemic reperfusion results in enhanced lipid peroxidation of cardiac membranes, which can be blocked by h-SOD, and therefore is most likely secondary to oxygen radical generation at reflow. (J. Clin.

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“…Effects of peroxidative damage on energy-linked functions and membrane enzymes of mitochondria were reported [2]. In the presence of pro-oxidants isolated mitochondria swell and lyse after incubation in salt media and concomitantly lipid peroxides were accumulated [3].…”

Section: Introductionmentioning

confidence: 99%