Effect of Cytochrome c on the Generation and Elimination of O<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif"><mml:msubsup><mml:mrow /><mml:mrow><mml:mn>2</mml:mn></mml:mrow><mml:mrow><mml:mo>⨪</mml:mo></mml:mrow></mml:msubsup></mml:math> and H2O2 in Mitochondria

Zhao, Yungang; Wang, Zhibo; Xu, Jie

doi:10.1074/jbc.m209681200

Cited by 126 publications

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“…The primary source of ROS in sperm is the respiratory chain of the mitochondrion (5)(6)(7)(8). The main ROS form in sperm is hydrogen peroxide (H 2 O 2 ), the concentration of which in sperm has not been measured (2)(3)(4), whereas in liver cells, the H 2 O 2 concentration (10 Ϫ7 to 10 Ϫ9 mol͞liter) is known to be 100-to 10,000-fold higher than that of superoxide (O 2 ⅐Ϫ ) (Ϸ10 Ϫ11 mol͞ liter) (6,9,10). O 2 ⅐Ϫ , as the precursor of H 2 O 2 and a short-lived ion, can be rapidly converted to H 2 O 2 by several pathways and does not accumulate in the cell (10,11).…”

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“…The main ROS form in sperm is hydrogen peroxide (H 2 O 2 ), the concentration of which in sperm has not been measured (2)(3)(4), whereas in liver cells, the H 2 O 2 concentration (10 Ϫ7 to 10 Ϫ9 mol͞liter) is known to be 100-to 10,000-fold higher than that of superoxide (O 2 ⅐Ϫ ) (Ϸ10 Ϫ11 mol͞ liter) (6,9,10). O 2 ⅐Ϫ , as the precursor of H 2 O 2 and a short-lived ion, can be rapidly converted to H 2 O 2 by several pathways and does not accumulate in the cell (10,11). The downstream ROS product of H 2 O 2 , namely hydroxyl radical (⅐OH), is highly reactive in directly inducing DNA single strand break and lipid peroxidation (12,13).…”

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confidence: 99%

“…Because H 2 O 2 can also diffuse freely among the membrane systems of the cell, making it the most prevalent ROS form (14), its reduction becomes a major challenge for the normal functions of the cell. Recently, it was demonstrated that the cytochrome c (Cc)-mediated electron-leak pathway can strongly suppress the formation of H 2 O 2 by the respiratory chain and efficiently destroy preexisting H 2 O 2 (10,15,16). Cc is thus considered a significant physiological contributor for H 2 O 2 detoxification in the cell (10,15,17).…”

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Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis

Liu

Lin

et al. 2006

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

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Hydrogen peroxide (H2O2) is the major reactive oxygen species (ROS) produced in sperm. High concentrations of H 2O2 in sperm induce nuclear DNA fragmentation and lipid peroxidation and result in cell death. The respiratory chain of the mitochondrion is one of the most productive ROS generating systems in sperm, and thus the destruction of ROS in mitochondria is critical for the cell. It was recently reported that H 2O2 generated by the respiratory chain of the mitochondrion can be efficiently destroyed by the cytochrome c-mediated electron-leak pathway where the electron of ferrocytochrome c migrates directly to H 2O2 instead of to cytochrome c oxidase. In our studies, we found that mouse testisspecific cytochrome c (T-Cc) can catalyze the reduction of H 2O2 three times faster than its counterpart in somatic cells (S-Cc) and that the T-Cc heme has the greater resistance to being degraded by H 2O2. Together, these findings strongly imply that T-Cc can protect sperm from the damages caused by H 2O2. Moreover, the apoptotic activity of T-Cc is three to five times greater than that of S-Cc in a well established apoptosis measurement system using Xenopus egg extract. The dramatically stronger apoptotic activity of T-Cc might be important for the suicide of male germ cells, considered a physiological mechanism that regulates the number of sperm produced and eliminates those with damaged DNA. Thus, it is very likely that T-Cc has evolved to guarantee the biological integrity of sperm produced in mammalian testis. mouse testis ͉ antioxidation

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Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis

Liu

Lin

et al. 2006

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

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“…Complex I and III of the ETC have been identified as the two principal sites of superoxide anion (O 2 -) generation [52]. While much of the O 2 -is released from complex III to either side of the inner membrane, the iron-sulfur cluster N 2 of complex I appears to be the main site of O 2 -release to the matrix [53]. The O 2 -so formed is disposed of by several pathways.…”

Section: Molecular Mechanisms Of Melatonin's Antiamyloid Actionsmentioning

confidence: 99%

Alzheimer’s Disease: Focus on the Neuroprotective Role of Melatonin

Srinivasan¹

2012

J Neurol Res

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Alzheimer's disease (AD) is characterized by a progressive loss of memory and cognitive function, and by behavioural and sleep disturbances, including insomnia. The pathophysiology of AD has been attributed to oxidative stress-induced amyloid-β protein (Aβ) deposition. Abnormal tau protein, mitochondrial dysfunction and protein hyper-phosphorylation have been demonstrated in neural tissues of AD patients. AD patients exhibit severe sleep-wake disturbances and these sleep disturbances are associated with rapid cognitive decline and memory impairment. Optimally effective management of AD patients will likely require a drug that can arrest Aβ -induced neurotoxic effects and can also restore the disturbed sleep-wake rhythm, with improvement in sleep quality. In this context, the pineal hormone melatonin has been demonstrated to be an effective antioxidant that can prevent Aβ -induced neurotoxic effects through a variety of mechanisms. Sleep deprivation itself produces many effects including oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, altered proteosomal processing and abnormal activation of enzymes. In addition to treating the signs and symptoms of AD, treatment of sleep disturbances may also be necessary for preventing and arresting AD progression. Besides melatonin, a number of melatonergic agonists such as ramelteon, agomelatine and tasimelteon are now used clinically for treating insomnia and other sleep disorders. Their use may also be beneficial in treating Alzheimer's disease.

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“…and H 2 O 2 in two electron leak pathways mediated by the cytochrome C [1][2][3]. Based on the involvement of the metabolic route of in mitochondria was defined by four electron leak pathways shown as in the red part of the ( Figure 1) [4].…”

Section: Introduction Four Electron Leak Pathways Of Mitochondrial Rementioning

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Ideas in Scientific Research on Human Health and Heart Care Raised from the Electron Leak Pathways of Mitochondrial Respiratory Chain

Xu¹

2016

J Clin Exp Cardiolog

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Respiratory chain is a group of redox enzymes located in the inner membrane of mitochondria. Mitochondria are the cellular "power house" to produce ATP through the way of electron transfer of the respiratory chain. In our lab, it is established that the production of ATP is always combined with the ROS (Reactive Oxygen Species) generation through the electron leak pathways. The confirmation of electron leak pathways of respiratory chain reveals that the efficiency of ATP production in mitochondria is strongly affected by the electron leakage of the respiratory chain-the more the electrons leaked the less the ATP produced. How the electron leak pathways related to aging and agerelated degenerative disease is a new investigative field of health and longevity. As the substrates of the respiratory chain (O 2 and nutrients) are delivered by heart pumping, the respiratory chain can be considered as the molecular heart or a life-engine, the human body can be considered as an aggregate of huge numbers of molecular hearts or life-engines. With this in mind some ideas about human health and heart care are presented here for discussion.

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Effect of Cytochrome c on the Generation and Elimination of O2⨪ and H2O2 in Mitochondria

Cited by 126 publications

References 26 publications

Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis

Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis

Alzheimer’s Disease: Focus on the Neuroprotective Role of Melatonin

Ideas in Scientific Research on Human Health and Heart Care Raised from the Electron Leak Pathways of Mitochondrial Respiratory Chain

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