Apoptosis: bombarding the mitochondria

2003 ◽  
Vol 39 ◽  
pp. 41-51 ◽  
Author(s):  
Philippe Parone ◽  
Muriel Priault ◽  
Dominic James ◽  
Steven F Nothwehr ◽  
Jean-Claude Martinou
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Membrane ◽  
Family Members ◽  
Reactive Oxygen ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Outer Mitochondrial Membrane ◽  
Caspase Activation ◽  
Mitochondrial Intermembrane Space ◽  
Death Signals

Mitochondria play a central role in apoptosis triggered by many stimuli. They integrate death signals through Bcl-2 family members and co-ordinate caspase activation through the release of apoptogenic factors that are normally sequestered in the mitochondrial intermembrane space. The release of these proteins is the result of the outer mitochondrial membrane becoming permeable. In addition, mitochondria can initiate apoptosis through the production of reactive oxygen species.

scholarly journals Kill one or kill the many: interplay between mitophagy and apoptosis

2020 ◽  
Vol 402 (1) ◽  
pp. 73-88
Author(s):  
Simone Wanderoy ◽  
J. Tabitha Hees ◽  
Ramona Klesse ◽  
Frank Edlich ◽  
Angelika B. Harbauer
Keyword(s):  
Mitochondrial Membrane ◽  
Current Knowledge ◽  
Special Focus ◽  
Intermembrane Space ◽  
Outer Mitochondrial Membrane ◽  
Caspase Activation ◽  
The Central Nervous System ◽  
Mitochondrial Intermembrane Space ◽  
Specialized Form ◽  
The Many

AbstractMitochondria are key players of cellular metabolism, Ca2+ homeostasis, and apoptosis. The functionality of mitochondria is tightly regulated, and dysfunctional mitochondria are removed via mitophagy, a specialized form of autophagy that is compromised in hereditary forms of Parkinson’s disease. Through mitophagy, cells are able to cope with mitochondrial stress until the damage becomes too great, which leads to the activation of pro-apoptotic BCL-2 family proteins located on the outer mitochondrial membrane. Active pro-apoptotic BCL-2 proteins facilitate the release of cytochrome c from the mitochondrial intermembrane space (IMS) into the cytosol, committing the cell to apoptosis by activating a cascade of cysteinyl-aspartate specific proteases (caspases). We are only beginning to understand how the choice between mitophagy and the activation of caspases is determined on the mitochondrial surface. Intriguingly in neurons, caspase activation also plays a non-apoptotic role in synaptic plasticity. Here we review the current knowledge on the interplay between mitophagy and caspase activation with a special focus on the central nervous system.

scholarly journals Peroxiredoxin-5 targeted to the mitochondrial intermembrane space attenuates hypoxia-induced reactive oxygen species signalling

2013 ◽  
Vol 456 (3) ◽  
pp. 337-346 ◽  
Author(s):  
Simran S. Sabharwal ◽  
Gregory B. Waypa ◽  
Jeremy D. Marks ◽  
Paul T. Schumacker
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Cellular Responses ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Mitochondrial Intermembrane Space ◽  
Ros Reactive Oxygen Species

This study demonstrates that peroxiredoxin-5 expression in the mitochondrial intermembrane space can scavenge mitochondrial ROS (reactive oxygen species) signals, thereby inhibiting hypoxia-induced cellular responses.

Oxygen-dependent activation of Cu,Zn-superoxide dismutase-1

Metallomics ◽  
2017 ◽  
Vol 9 (8) ◽  
pp. 1047-1059 ◽  
Author(s):  
Morgan M. Fetherolf ◽  
Stefanie D. Boyd ◽  
Duane D. Winkler ◽  
Dennis R. Winge
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Reactive Oxygen ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Superoxide Dismutase 1 ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc ◽  
Mitochondrial Intermembrane Space

Copper zinc superoxide dismutase (Sod1) is a critical enzyme in limiting reactive oxygen species in both the cytosol and the mitochondrial intermembrane space.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

2001 ◽  
Vol 280 (1) ◽  
pp. L10-L17 ◽  
Author(s):  
Han-Ming Shen ◽  
Zhuo Zhang ◽  
Qi-Feng Zhang ◽  
Choon-Nam Ong
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Alveolar Macrophages ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Parp Cleavage ◽  
Oxygen Species ◽  
Caspase Activation ◽  
Caspase 9 ◽  
Induced Apoptosis

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

scholarly journals The toxic effect of Vu-Defr, a defensin from Vigna unguiculata seeds, on Leishmania amazonensis is associated with reactive oxygen species production, mitochondrial dysfunction, and plasma membrane perturbation

2018 ◽  
Vol 64 (7) ◽  
pp. 455-464 ◽  
Author(s):  
Géssika Silva Souza ◽  
Lais Pessanha de Carvalho ◽  
Edésio José Tenório de Melo ◽  
Valdirene Moreira Gomes ◽  
André de Oliveira Carvalho
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Membrane ◽  
Biological Activities ◽  
Reactive Oxygen ◽  
Leishmania Amazonensis ◽  
New Drugs ◽  
Oxygen Species ◽  
Membrane Perturbation ◽  
Plant Defensins

Plant defensins are plant antimicrobial peptides that present diverse biological activities in vitro, including the elimination of Leishmania amazonensis. Plant defensins are considered promising candidates for the development of new drugs. This protozoan genus has great epidemiological importance and the mechanism behind the protozoan death by defensins is unknown, thus, we chose L. amazonensis for this study. The aim of the work was to analyze the possible toxic mechanisms of Vu-Defr against L. amazonensis. For analyses, the antimicrobial assay was repeated as previously described, and after 24 h, an aliquot of the culture was tested for viability, membrane perturbation, mitochondrial membrane potential, reactive oxygen species (ROS) and nitric oxide (NO) inductions. The results of these analyses indicated that after interaction with L. amazonensis, the Vu-Defr causes elimination of promastigotes from culture, membrane perturbation, mitochondrial membrane collapse, and ROS induction. Our analysis demonstrated that NO is not produced after Vu-Defr and L. amazonensis interaction. In conclusion, our work strives to help to fill the gap relating to effects caused by plant defensins on protozoan and thus better understand the mechanism of action of this peptide against L. amazonensis.

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