Outer mitochondrial membrane permeabilization: an open-and-shut case?

Robertson, Janet; Zhivotovsky, Boris; Gogvadze, Vladimir; Orrenius, Sten

doi:10.1038/sj.cdd.4401218

Cited by 25 publications

(14 citation statements)

References 28 publications

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“…This is mainly due to Bax/Bak effect on ROS generation and peroxidase activation of cyt c. This molecular scenario portrays the link between proteins of Bcl-2 family and CL peroxidation in the regulation of release of cyt c during apoptosis. The detailed mechanisms through which oxidized CL induces permeabilization of mitochondria still remain elusive, although several models have been proposed [5,6,11,29]. The fact that the recombinant Bax induced a release of Smac/Diablo from non-energized mitochondria similarly to cyt c (Fig.…”

Section: Recombinant Bax Increases Mitochondrial Peroxidase Activitymentioning

confidence: 99%

Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis

Jiang¹,

Huang²,

Zhao³

et al. 2008

Biochemical and Biophysical Research Communications

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Bax/Bak activation and cardiolipin peroxidation are essential for cytochrome c release during apoptosis, yet, the link between them remains elusive. We report that sequence of events after exposure of mouse embryonic fibroblast (MEF) cells to actinomycin D followed the order: Bax translocation -> superoxide production -> cardiolipin peroxidation. Genetic ablation of Bax/Bak inhibited actinomycin D induced superoxide production and cardiolipin peroxidation. Rotenone caused robust superoxide generation but did not trigger cardiolipin peroxidation in Bax/Bak double knockout MEF cells. This suggests that, in addition to participating in ROS generation, Bax/Bak play another specific role in cardiolipin oxidation. In isolated mitochondria, recombinant Bax enhanced succinate induced cardiolipin oxidation and cytochrome c release. Mitochondrial peroxidase activity, likely involved in cardiolipin peroxidation, was enhanced upon incubation with recombinant Bax. Thus cardiolipin peroxidation may be causatively and time-dependently related to Bax/Bak effects on ROS generation and peroxidase activation of cytochrome c.

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Section: Recombinant Bax Increases Mitochondrial Peroxidase Activitymentioning

confidence: 99%

Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis

Jiang¹,

Huang²,

Zhao³

et al. 2008

Biochemical and Biophysical Research Communications

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“…4E-H). Because loss of mitochondrial membrane potential preceded cytochrome c release on g-irradiation, permeability transition pore activation may be involved in the release of cytochrome c under these conditions (29). Alternatively, mitochondrial cytochrome c release on g-irradiation may occur by mechanism(s) not involving permeability transition (29).…”

Section: Sensitization For G-irradiationmentioning

confidence: 99%

Sensitization for γ-Irradiation–Induced Apoptosis by Second Mitochondria-Derived Activator of Caspase

et al. 2005

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Resistance to current treatment regimens, such as radiation therapy, remains a major concern in oncology and may be caused by defects in apoptosis programs. Because inhibitor of apoptosis proteins (IAPs), which are expressed at high levels in many tumors, block apoptosis at the core of the apoptotic machinery by inhibiting caspases, therapeutic modulation of IAPs could target a key control point in resistance. Here, we report for the first time that full-length or mature second mitochondria-derived activator of caspase (Smac), an inhibitor of IAPs, significantly enhanced ;-irradiation-induced apoptosis and reduced clonogenic survival in neuroblastoma, glioblastoma, or pancreatic carcinoma cells. Notably, Smac had no effect on DNA damage/DNA repair, activation of nuclear factor-KB, up-regulation of p53 and p21 proteins, or cell cycle arrest following ;-irradiation, indicating that Smac did not alter the initial damage and/or cellular stress response. Smac enhanced activation of caspase-2, caspase-3, caspase-8, and caspase-9, loss of mitochondrial membrane potential, and cytochrome c release on ;-irradiation. Inhibition of caspases also blocked ;-irradiation-induced mitochondrial perturbations, indicating that Smac facilitated caspase activation, which in turn triggered a mitochondrial amplification loop. Interestingly, mitochondrial perturbations were completely blocked by the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone or the relatively selective caspase-2 inhibitor N-benzyloxycarbonylVal-Asp-Val-Ala-Asp-fluoromethylketone, whereas caspase-8 or caspase-3 inhibitors only inhibited the increased drop of mitochondrial membrane potential provided by Smac, suggesting that caspase-2 was acting upstream of mitochondria after ;-irradiation. In conclusion, our findings provide evidence that targeting IAPs (e.g., by Smac agonists) is a promising strategy to enhance radiosensitivity in human cancers. (Cancer Res 2005; 65(22): 10502-13)

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“…Mitochondria accumulate large amounts of Ca 2ϩ with simultaneous uptake of P i and precipitation in the matrix of an insoluble salt similar to hydroxylapatite, in a way that the ionic Ca 2ϩ concentration in the matrix is only moderately altered (26). Another route of Ca 2ϩ uptake is functionally related with the opening of the Ca 2ϩ -mediated permeability pore (136), a sudden increase in inner membrane permeability induced by a large series of compounds that collapses membrane potential and permits the efflux and influx of large molecules and ions. Intramitochondrial Ca 2ϩ is recognized as an allosteric activator of matrix dehydrogenases, such as NAD ϩ -isocitrate dehydrogenase, pyruvate dehydrogenase and ␣-ketoglutarate dehydrogenase (104) and as co-factor of mitochondrial nitric oxide (NO) synthase (mtNOS) (59).…”

Section: Electrochemical Potential and F 1 -Atpase Molecular Rotor Armentioning

confidence: 99%

The mitochondrial energy transduction system and the aging process

Navarro¹,

Boveris²

2007

American Journal of Physiology-Cell Physiology

590

401

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Navarro A, Boveris A. The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292: C670 -C686, 2007; doi:10.1152/ajpcell.00213.2006.-Aged mammalian tissues show a decreased capacity to produce ATP by oxidative phosphorylation due to dysfunctional mitochondria. The mitochondrial content of rat brain and liver is not reduced in aging and the impairment of mitochondrial function is due to decreased rates of electron transfer by the selectively diminished activities of complexes I and IV. Inner membrane H ϩ impermeability and F1-ATP synthase activity are only slightly affected by aging. Dysfunctional mitochondria in aged rodents are characterized, besides decreased electron transfer and O 2 uptake, by an increased content of oxidation products of phospholipids, proteins and DNA, a decreased membrane potential, and increased size and fragility. Free radicalmediated oxidations are determining factors of mitochondrial dysfunction and turnover, cell apoptosis, tissue function, and lifespan. Inner membrane enzyme activities, such as those of complexes I and IV and mitochondrial nitric oxide synthase, decrease upon aging and afford aging markers. The activities of these three enzymes in mice brain are linearly correlated with neurological performance, as determined by the tightrope and the T-maze tests. The same enzymatic activities correlated positively with mice survival and negatively with the mitochondrial content of lipid and protein oxidation products. Conditions that increase survival, as vitamin E dietary supplementation, caloric restriction, high spontaneous neurological activity, and moderate physical exercise, ameliorate mitochondrial dysfunction in aged brain and liver. The pleiotropic signaling of mitochondrial H 2O2 and nitric oxide diffusion to the cytosol seems modified in aged animals and to contribute to the decreased mitochondrial biogenesis in old animals. oxidative damage; survival; complexes I and IV; nitric oxide synthase EARLY OBSERVATIONS by Leloir and Muñoz (92) indicated that fatty acid oxidation depends on a labile particulate material of liver homogenates. Later, Kennedy and Lehninger (82) reported that the oxidation of fatty acids and of citric acid cycle intermediates was carried out by osmotically active structures with coupled ADP phosphorylation to ATP. Simultaneously, Sjostrand (146) and Palade (126) recognized by electron microscopy the characteristic double membrane of mitochondria. The concept of oxidative phosphorylation as the mitochondrial function evolved from the confluence of structural and biochemical knowledge and by 1952, mitochondria were described by Lehninger (91) as intracellular "power plants".

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Outer mitochondrial membrane permeabilization: an open-and-shut case?

Cited by 25 publications

References 28 publications

Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis

Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis

Sensitization for γ-Irradiation–Induced Apoptosis by Second Mitochondria-Derived Activator of Caspase

The mitochondrial energy transduction system and the aging process

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