The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant

@article{Goldstein2000TheCR,
  title={The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant},
  author={Joshua C. Goldstein and Nigel J. Waterhouse and P. Juin and Gerard I. Evan and Douglas R. Green},
  journal={Nature Cell Biology},
  year={2000},
  volume={2},
  pages={156-162}
}
Release of cytochrome c from mitochondria triggers activation of caspase proteases and death of a cell by apoptosis. However, the mechanism and kinetics of cytochrome c release remain unknown. Here we study this event by using green fluorescent protein (GFP)-tagged cytochrome c, and find that the release of cytochrome-c–GFP always precedes exposure of phosphatidylserine and the loss of plasma-membrane integrity — characteristics of apoptotic cells. Once initiated, the release of cytochrome-c… 
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Cytochrome c is released in a single step during apoptosis
TLDR
There is a general mechanism responsible for cytochrome c release that proceeds in a single step that is independent of changes in mitochondrial membrane potential (ΔΨm), and this paper concludes that this mechanism is responsible for apoptotic signaling.
On the Release of Cytochrome c from Mitochondria during Cell Death Signaling
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This work reviews the process in terms of the influences that induce mitochondria to release cyt c, the possible mechanisms of such release and the downstream consequences for caspase activation, and focuses on technical methods of determining cyt c release.
Different mitochondrial intermembrane space proteins are released during apoptosis in a manner that is coordinately initiated but can vary in duration.
TLDR
In situ fluorescent labeling of proteins tagged with a short tetracysteine-containing sequence to follow the release of Smac, Omi, adenylate kinase-2, cytochrome c, and apoptosis-inducing factor during apoptosis suggest that these proteins are released through the same mitochondrial pore and that apoptosis may not be regulated through a selective release of individual mitochondrial proteins.
Mechanisms of cytochrome c release from mitochondria
TLDR
Cyt c has been associated also to vital cell functions (i.e. differentiation), suggesting that its release not always occurs in an all-or-nothing fashion and that mitochondrial outer membrane permeabilization may not invariably lead to cell death.
Temporal relationship between cytochrome c release and mitochondrial swelling during UV-induced apoptosis in living HeLa cells.
TLDR
Evidence is found that cytochrome c was also released before mitochondrial swelling in apoptosis induced by other cell death-inducing treatments, including tumor necrosis factor (TNF) and actinomycin D.
The Role of the Mitochondrial Apoptosis Induced Channel MAC in Cytochrome c Release
TLDR
The mitochondrial apoptosis-induced channel, MAC, is a high-conductance channel that forms during early apoptosis and is the putative cytochrome c release channel and unlike activation of the permeability transition pore, MAC formation occurs without loss of outer membrane integrity and depolarization.
Preservation of Mitochondrial Structure and Function after Bid- or Bax-Mediated Cytochrome c Release
TLDR
It is shown that recombinant Bid and Bax cause complete cytochrome c loss from isolated mitochondria in vitro, but preserve the ultrastructure and protein import function of mitochondria, which depend on inner membrane polarization.
Cytochrome C Maintains Mitochondrial Transmembrane Potential and Atp Generation after Outer Mitochondrial Membrane Permeabilization during the Apoptotic Process
TLDR
It is found that when caspase activity is inhibited, mitochondrial outer membrane permeabilization causes a rapid depolarization of mitochondrial transmembrane potential, which recovers to original levels over the next 30–60 min and is then maintained.
Multiple kinetics of mitochondrial cytochrome c release in drug-induced apoptosis.
TLDR
The data indicate the existence of multiple kinetics of cytochrome c release in drug-induced apoptosis, which was also released out of the cell into the extracellular space before loss of plasma membrane integrity.
Smac/DIABLO and cytochrome c are released from mitochondria through a similar mechanism during UV-induced apoptosis
TLDR
In HeLa cells, both Smac and Cyt-c are released from mitochondria during UV-induced apoptosis through the same permeability transition mechanism, which the authors believe is triggered by the aggregation of Bax in the outer mitochondrial membrane to form lipid-protein complex.
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