Cardiolipin oxidation sets cytochrome c free

  title={Cardiolipin oxidation sets cytochrome c free},
  author={Sten Orrenius and Boris Zhivotovsky},
  journal={Nature Chemical Biology},
Cytochrome c release from the mitochondria is a critical component of the apoptotic cell-death program. Cytochrome c–catalyzed peroxidation of cardiolipin, a mitochondrial phospholipid, has now been shown to lessen the binding of cytochrome c to the mitochondrial inner membrane and facilitate permeabilization of the outer membrane. These results describe a new and earlier pro-apoptotic role for cytochrome c. 

Cardiolipin deficiency releases cytochrome c from the inner mitochondrial membrane and accelerates stimuli-elicited apoptosis

Cardiolipin (CL) is a mitochondria-specific phospholipid synthesized by CL synthase (CLS). We describe here a human gene for CLS and its analysis via RNAi knockdown on apoptotic progression. Although

Identifying the role of cytochrome c in post-resuscitation pathophysiology.

Mechanisms of cytochrome c release from mitochondria

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.

Free radical oxidation of cardiolipin: chemical mechanisms, detection and implication in apoptosis, mitochondrial dysfunction and human diseases

The free radical oxidation products of CL have been emerged as important mediators in apoptosis and the implication of CL oxidation in mitochondria-mediated apoptosis, mitochondrial dysfunction and human diseases is suggested.

Cardiolipin and Its Different Properties in Mitophagy and Apoptosis

The unique structural features of CL as well as the current understanding of CL-based molecular mechanisms of mitophagy and apoptosis are discussed.

Raman Spectroscopy Reveals Selective Interactions of Cytochrome c with Cardiolipin That Correlate with Membrane Permeability.

Cytochrome-induced permeabilization proceeds through selective interaction of cytochrome c with cardiolipin, resulting in protein unfolding, where the unfolded form interacts with cardiolaipin acyl chains within the bilayer to induce permeability.

Curvature-Dependent Binding of Cytochrome c to Cardiolipin.

The results show that membrane curvature qualitatively affects peripheral protein-lipid interactions and also highlights the disparity between in vitro binding studies and their physiological counterparts where cone-shaped lipids, like cardiolipin, are involved.

Cardiolipin plays a role in KCN-induced necrosis.

Cardiolipin at the heart of stress response across kingdoms

These studies showed that cardiolipin is not only important for mitochondrial ultrastructure and for the stability of respiratory complexes, but it is also a key player in the response to stress, the formation of reactive oxygen species, and the execution of programmed cell death.



Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors

Insight is provided into the role of reactive oxygen species in triggering the cell-death pathway and an early role for cytochrome c before caspase activation is described.

Loss of molecular interaction between cytochrome c and cardiolipin due to lipid peroxidation.

This finding suggests that the peroxidation of CL induces a release of cytochrome c from mitochondria into the cytosol, which release induces apoptosis in the cells.

Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis.

The results suggest that phosphatidylglycerol saturation and subsequent decreases in cardiolipin affect the association of cy tochrome c with the inner mitochondrial membrane, directly influencing the pathway to cytochrome c release and subsequent apoptosis.

Cytochrome c release from mitochondria proceeds by a two-step process

The results indicate that the release of cytochrome c involves a distinct two-step process that is undermined when either step is compromised, and this mechanism also extends to conditions of mitochondrial permeability transition insofar as cy tochrome c release is significantly depressed when the electrostatic interaction between cyto Chrome c and cardiolipin remains intact.

Caspase-2 Permeabilizes the Outer Mitochondrial Membrane and Disrupts the Binding of Cytochrome c to Anionic Phospholipids*

Together, the data suggest that caspase-2 possesses an unparalleled ability to engage the mitochondrial apoptotic pathway by permeabilizing the outer mitochondrial membrane and/or by breaching the association of cytochrome c with the inner mitochondrial membrane.

Mitochondrial phospholipid hydroperoxide glutathione peroxidase inhibits the release of cytochrome c from mitochondria by suppressing the peroxidation of cardiolipin in hypoglycaemia-induced apoptosis.

Findings suggest that the generation of CL-OOH in mitochondria might be a primary event that triggers the release of cyt.

Cardiolipin provides specificity for targeting of tBid to mitochondria

Evidence is provided that cardiolipin, which is present in mitochondrial membranes, mediates the targeting of tBid to mitochondria through a previously unkown three-helix domain in tBID, which implicate cardiolIPin in the pathway for cytochrome c release.

The Pathophysiology of Mitochondrial Cell Death

The therapeutic induction of MOMP may restore apoptosis in cancer cells in which it is disabled, and the general rules governing the pathophysiology and controversial issues regarding its regulation are discussed.

Peroxiredoxin III, a Mitochondrion-specific Peroxidase, Regulates Apoptotic Signaling by Mitochondria*

The results suggest that Prx III is a critical regulator of the abundance of mitochondrial H2O2, which itself promotes apoptosis in cooperation with other mediators of apoptotic signaling.

Lack of Mitochondrial Anionic Phospholipids Causes an Inhibition of Translation of Protein Components of the Electron Transport Chain

The molecular basis for the lack of mitochondrial function in PGs1Δ cells is the failure to translate gene products essential to the electron transport chain.