Electron flow into cytochrome c coupled with reactive oxygen species from the electron transport chain converts cytochrome c to a cardiolipin peroxidase: role during ischemia–reperfusion

Aluri, Hema; Simpson, David C.; Allegood, Jeremy C.; Hu, Ying; Szczepanek, Karol; Gronert, Scott; Chen, Qun; Lesnefsky, Edward J.

doi:10.1016/j.bbagen.2014.07.017

Cited by 32 publications

(25 citation statements)

References 59 publications

(98 reference statements)

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“…Recent studies showed increase in oxidation of Met 80 to the Met 80 -sulfoxide (Met 80 -O), and loss of cardiolipin in the ischemic isolated hearts after 30 min of reperfusion [24]. Since Met 80 can only undergo self-oxidation when it is not coordinating the heme Fe [19], these results support ex vivo formation of pentacoordinated cyt c during ischemia-reperfusion.…”

Section: Introductionmentioning

confidence: 80%

“…Cyt c oxygenase or peroxidase activity has not been demonstrated in vivo , but the presence of Met-O cyt c supports the existence of oxygenase/peroxidase activity, which can account for cristae degradation. Degeneration of mitochondrial morphology, especially cristaeolysis, is commonly observed in ischemic mitochondria [3, 19, 24]. Peroxidized cardiolipin can further elicit a free radical chain reaction even without further ROS production.…”

Section: Discussionmentioning

confidence: 99%

“…Since Met 80 can only undergo self-oxidation when it is not coordinating the heme Fe [19], these results support ex vivo formation of pentacoordinated cyt c during ischemia-reperfusion. Using normal isolated mitochondria, these investigators proposed that electron flow through cyt c , coupled with excessive ROS production, is required for the oxidation of Met 80 [24]. However, the conditions required for cyt c Met-O formation and ROS formation in isolated mitochondria are not the same [24], so it remains uncertain whether inhibition of ET or excessive ROS, or both required for Met-O formation and peroxidase activity.…”

Section: Introductionmentioning

confidence: 99%

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Disruption of cytochrome c heme coordination is responsible for mitochondrial injury during ischemia

Birk

Chao

Liu

et al. 2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Background It was recently suggested that electron flow into cyt c, coupled with ROS generation, oxidizes cyt c Met80 to Met80 sulfoxide (Met-O) in isolated hearts after ischemia-reperfusion, and converts cyt c to a peroxidase. We hypothesize that ischemia disrupts Met80-Fe ligation of cyt c, forming pentacoordinated heme Fe2+, which inhibits electron transport (ET) and promotes oxygenase activity. Methods SS-20 (Phe-D-Arg-Phe-Lys-NH2) was used to demonstrate the role of Met80-Fe ligation in ischemia. Mitochondria were isolated from ischemic rat kidneys to determine sites of respiratory inhibition. Mitochondrial cyt c and cyt c Met-O were quantified by western blot, and cristae architecture was examined by electron microscopy. Results Biochemical and structural studies showed that SS-20 selectively targets cardiolipin (CL) and protects Met80-Fe ligation in cyt c. Ischemic mitochondria showed 17-fold increase in Met-O cyt c, and dramatic cristaeolysis. Loss of cyt c was associated with proteolytic degradation of OPA1. Ischemia significantly inhibited ET initiated by direct reduction of cyt c and coupled respiration. All changes were prevented by SS-20. Conclusion Our results show that ischemia disrupts the Met80-Fe ligation of cyt c resulting in formation of a globin-like pentacoordinated heme Fe2+ that inhibits ET, and converts cyt c into an oxygenase to cause CL peroxidation and proteolytic degradation of OPA1, resulting in cyt c release. General significance Cyt c heme structure represents a novel target for minimizing ischemic injury. SS-20, which we show to selectively target CL and protect the Met80-Fe ligation, minimizes ischemic injury and promotes ATP recovery.

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Section: Introductionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disruption of cytochrome c heme coordination is responsible for mitochondrial injury during ischemia

Birk

Chao

Liu

et al. 2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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“…Age-dependent loss of CL may be due to oxidative stress [72], which can be due to extrinsic ROS or by peroxidase activity of cytochrome C that is closely associated with CL [73]. Prevention of peroxidation of CL may attenuate or abrogate mitochondrial dysfunction [73]. In the brain, melatonin might help to preserve the structural integrity of cardiolipin by preventing age-related peroxidation of the cardiolipin [74].…”

Section: Mitochondrial Structural Changes With Ageingmentioning

confidence: 99%

Mitochondrial dysfunction in cardiac aging

Tocchi

Quarles

Basisty

et al. 2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

119

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Cardiovascular diseases are the leading cause of death in most developed nations. While it has received the least public attention, aging is the dominant risk factor for developing cardiovascular diseases, as the prevalence of cardiovascular diseases increases dramatically with increasing age. Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. Mitochondria play a great role in these processes, as cardiac function is an energetically demanding process. In this review, we examine mitochondrial dysfunction in cardiac aging. Recent research has demonstrated that mitochondrial dysfunction can disrupt morphology, signaling pathways, and protein interactions; conversely, mitochondrial homeostasis is maintained by mechanisms that include fission/fusion, autophagy, and unfolded protein responses. Finally, we describe some of the recent findings in mitochondrial targeted treatments to help meet the challenges of mitochondrial dysfunction in aging.

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“…ROS are formed in the path of abiotic processes but also by living cells themselves, for example through photosynthesis and the activity of the respiratory electron transport chain in mitochondria and bacterial cytoplasmic membranes [1, 2]. As such, ROS cause damage to most, if not all, biomolecules [3, 4], including oxidation of amino acids, vitamins, lipids, nucleotides, and DNA, with damage to the later promoting mutations [5].…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

<b><i>Salmonella</i></b> and Reactive Oxygen Species: A Love-Hate Relationship

Rhen¹

2019

J Innate Immun

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Salmonella enterica represents an enterobacterial species including numerous serovars that cause infections at, or initiated at, the intestinal epithelium. Many serovars also act as facultative intracellular pathogens with a tropism for phagocytic cells. These bacteria not only survive in phagocytes but also undergo de facto replication therein. Phagocytes, through the activities of phagocyte NADPH-dependent oxidase and inducible nitric oxide synthase, are very proficient in converting molecular oxygen to reactive oxygen (ROS) and nitrogen species (RNS). These compounds represent highly efficient effectors of the innate immune defense. Salmonella is by no means resistant to these effectors, which may stand in contrast to the host niches chosen. To cope with this paradox, these bacteria rely on an array of detoxification and repair systems. Combination these systems allows for a high enough tolerance to ROS and RNS to enable establishment of infection. In addition, salmonella possesses protein factors that have the potential to dampen the infection-associated inflammation, which evidently results in a reduced exposure to ROS and RNS. This review attempts to summarize the activities and strategies by which salmonella tries to cope with ROS and RNS and how the bacterium can make use of these innate defense factors.

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Electron flow into cytochrome c coupled with reactive oxygen species from the electron transport chain converts cytochrome c to a cardiolipin peroxidase: role during ischemia–reperfusion

Cited by 32 publications

References 59 publications

Disruption of cytochrome c heme coordination is responsible for mitochondrial injury during ischemia

Disruption of cytochrome c heme coordination is responsible for mitochondrial injury during ischemia

Mitochondrial dysfunction in cardiac aging

<b><i>Salmonella</i></b> and Reactive Oxygen Species: A Love-Hate Relationship

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