Membrane lipids and cell death: an overview

Cristea, Ileana M.; Esposti, Mauro Degli

doi:10.1016/j.chemphyslip.2004.02.002

Cited by 76 publications

(71 citation statements)

References 271 publications

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“…To this end, we performed mass spectrometric analysis of mitochondrial lipids from murine liver and brain. 22 Detailed analysis of electrospray profiles revealed an increase in peroxidized lipid species in both brain and liver mitochondria from HtrA2 KO mice (Table 3), thereby suggesting an enhanced ROS-mediated damage to membrane lipids in these animals. Consequently, loss of HtrA2 appears to trigger accumulation of oxidative stress at both the protein and lipid levels.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response

et al. 2008

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Cellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here, we demonstrate that loss of HtrA2 results in transcriptional upregulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinson's disease patients' brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response

et al. 2008

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“…Subsequently several studies revealed that apoptosis correlated with a progressive proliferation of intracellular membranes leading to the formation of apoptotic blebs. This was in contrast to the process of necrosis, as apoptotic cells disintegrate without leaking their intracellular contents out in the medium, preventing the inflammatory reactions that are induced by necrotic cells (Cristea and Degli Esposti, 2004). Modifications of lipid composition and bilayer curvature of the mitochondrial membranes seem to be crucial for permeabilization.…”

Section: Importance Of Lipids and Membrane Topologymentioning

confidence: 99%

“…The classic models mentioned above are far from being complete, and theories on the molecular mechanism are formulated, debated and modified on a regular basis (LuckenArdjomande and Martinou, 2005a). Recent investigations revealed that during apoptosis, the mitochondrial membrane properties are profoundly modified and the mitochondrial network undergoes extensive fragmentation Cristea and Degli Esposti, 2004). Mitochondrial membrane permeabilization requires drastic membrane remodelling, and both lipids and components of the fission/fusion machinery may participate in this process.…”

Section: Mitochondrial Membrane Permeabilizationmentioning

confidence: 99%

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Mitochondria and cancer: is there a morphological connection?

2006

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Mitochondria are key players in several cellular functions including growth, division, energy metabolism, and apoptosis. The mitochondrial network undergoes constant remodelling and these morphological changes are of direct relevance for the role of this organelle in cell physiology. Mitochondrial dysfunction contributes to a number of human disorders and may aid cancer progression. Here, we summarize the recent contributions made in the field of mitochondrial dynamics and discuss their impact on our understanding of cell function and tumorigenesis.

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“…Moreover, if the CL required for OM pore formation were in its native state, this would be inconsistent with the reported loss of CL during apoptosis (22)(23)(24). In addressing these questions, various investigators have suggested that CL or some modified form of CL existing at IM-OM contact sites is sufficient for apoptotic tBid recruitment (25,26). It has also been proposed that CL and/or its lyso-derivatives can redistribute from IM to OM in cells exposed to apoptotic stresses (27,28).…”

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confidence: 99%

Permeabilization of the Mitochondrial Outer Membrane by Bax/Truncated Bid (tBid) Proteins as Sensitized by Cardiolipin Hydroperoxide Translocation

Korytowski

Basova

Piłat

et al. 2011

Journal of Biological Chemistry

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Cytochrome c (cyt c) release upon oxidation of cardiolipin (CL) in the mitochondrial inner membrane (IM) under oxidative stress occurs early in the intrinsic apoptotic pathway. We postulated that CL oxidation mobilizes not only cyt c but also CL itself in the form of hydroperoxide (CLOOH) species. Relatively hydrophilic CLOOHs could assist in apoptotic signaling by translocating to the outer membrane (OM), thus promoting recruitment of the pro-apoptotic proteins truncated Bid (tBid) and Bax for generation of cyt c-traversable pores. Initial testing of these possibilities showed that CLOOH-containing liposomes were permeabilized more readily by tBid plus Ca 2؉ than CL-containing counterparts. Moreover, CLOOH translocated more rapidly from IM-mimetic to OM-mimetic liposomes than CL and permitted more extensive OM permeabilization. We found that tBid bound more avidly to CLOOH-containing membranes than to CL counterparts, and binding increased with increasing CLOOH content. Permeabilization of CLOOH-containing liposomes in the presence of tBid could be triggered by monomeric Bax, consistent with tBid/Bax cooperation in pore formation. Using CL-null mitochondria from a yeast mutant, we found that tBid binding and cyt c release were dramatically enhanced by transfer acquisition of CLOOH. Additionally, we observed a pre-apoptotic IM-to-OM transfer of oxidized CL in cardiomyocytes treated with the Complex III blocker, antimycin A. These findings provide new mechanistic insights into the role of CL oxidation in the intrinsic pathway of oxidative apoptosis.Cytochrome c (cyt c) 2 dissociation from the mitochondrial inner membrane (IM), movement into the intermembrane space, and then release into cytosol is recognized as a key early event in the intrinsic (mitochondrion-initiated) pathway of oxidative stress-induced apoptosis (1-3). How this occurs is still not completely understood, but accumulating evidence suggests that oxidative modification of cardiolipin (CL), e.g. conversion to hydroperoxide species (CLOOHs), plays an important role (4 -7). CL (diphosphatidylglycerol) is located primarily in the mitochondrial IM of normal eukaryotic cells, where it interacts with and supports the functions of cyt c, Complex III (cytochromes b and c 1 ), and Complex IV (cytochrome c oxidase) (8). Unlike most other phospholipids in which only the sn-2 fatty acyl group is unsaturated, both sn-1 and sn-2 groups of natural CL are typically unsaturated. In mammalian heart, for example, tetra-linoleoyl CL composes 75-80% of overall CL molecular species (9). Consequently, CL oxidizability and -OOH content per average oxidized molecule are typically much higher than for more conventional phospholipids such as those in the phosphatidylcholine and phosphatidylethanolamine families. Model studies with bovine heart CL in thin film or liposomal form have shown that its normally strong interaction with some fraction of IM cyt c is progressively weakened with increasing -OOH content (4), suggesting possible involvement in pro-apoptotic cyt c releas...

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Membrane lipids and cell death: an overview

Cited by 76 publications

References 271 publications

Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response

Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response

Mitochondria and cancer: is there a morphological connection?

Permeabilization of the Mitochondrial Outer Membrane by Bax/Truncated Bid (tBid) Proteins as Sensitized by Cardiolipin Hydroperoxide Translocation

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