2013
DOI: 10.1371/journal.pone.0069492
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Lytic and Non-Lytic Permeabilization of Cardiolipin-Containing Lipid Bilayers Induced by Cytochrome c

Abstract: The release of cytochrome c (cyt c) from mitochondria is an important early step during cellular apoptosis, however the precise mechanism by which the outer mitochondrial membrane becomes permeable to these proteins is as yet unclear. Inspired by our previous observation of cyt c crossing the membrane barrier of giant unilamellar vesicle model systems, we investigate the interaction of cyt c with cardiolipin (CL)-containing membranes using the innovative droplet bilayer system that permits electrochemical meas… Show more

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Cited by 13 publications
(24 citation statements)
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“…Furthermore, the larger size of DPG means that there will be fewer intramolecular spaces for MIMs to occupy, and local concentrations of MIM may be higher in the intermolecular spaces of DPG for a given surface area than for single-head phospholipids. In short, the geometry of DPG causes it to have a preference for negative curvature, and when it exists in a planar bilayer, it is more prone to undergo conformational changes in response to perturbations, an assertion which is supported by the solvatochromic effects observed with model membranes (Table 4) (38,(47)(48)(49).…”
Section: Aminoacylated Phospholipidsmentioning
confidence: 89%
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“…Furthermore, the larger size of DPG means that there will be fewer intramolecular spaces for MIMs to occupy, and local concentrations of MIM may be higher in the intermolecular spaces of DPG for a given surface area than for single-head phospholipids. In short, the geometry of DPG causes it to have a preference for negative curvature, and when it exists in a planar bilayer, it is more prone to undergo conformational changes in response to perturbations, an assertion which is supported by the solvatochromic effects observed with model membranes (Table 4) (38,(47)(48)(49).…”
Section: Aminoacylated Phospholipidsmentioning
confidence: 89%
“…Furthermore, the importance of DPG content in antimicrobial susceptibility has been demonstrated using model membrane systems (20,(42)(43)(44)(45). Additionally, apoptosis in mitochondria has been shown to be inextricably linked to DPG and its affinity for cytochrome c, with the DPG content increasing from Ϸ4% to in excess of 20% immediately prior to apoptosis (45)(46)(47). Therefore, the increased content of DPG in Gram-positive microbial membranes likely underlies the sensitivity of Gram-positive organisms to OPV-COEs.…”
Section: Aminoacylated Phospholipidsmentioning
confidence: 99%
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“…Indeed, RNAi knockdown of phospholipid scramblase 3 (PLS3) profoundly decreased the delivery of injured mitochondria to autophagosomes (Chu et al, 2013). While the (trans)-mitochondrial localization of PLS3 has not yet been firmly established (Korytowski et al, 2011), it is also possible that other intermembrane space proteins (including cytochrome c) (Xu et al, 2013) and integral OMM proteins - capable of binding CL - including members of Bcl-2 family (Asciolla et al, 2012; Epand et al, 2003; Ott et al, 2009) and voltage-dependent anion channel (VDAC) (Rostovtseva and Bezrukov, 2008) - may facilitate its redistribution to the mitochondrial surface (Garcia Fernandez et al, 2002). Importantly, autophageal machinery recognizes CLs more effectively than its metabolites, including mono- and di-lyso-CLs as well as CL oxidation products (Chu et al, 2013).…”
Section: Reduced Trans-membrane Asymmetry and Externalization Of Cls mentioning
confidence: 99%
“…This relates to i) identification of one or more individual molecular species of peroxidized CLs (CLox) from their highly diversified multiple forms accumulating during apoptosis (Domingues et al, 2008; Ji et al, 2012; Tyurin et al, 2010; see Tyurina et al, in this issue), and ii) the necessity and identity of potential protein partners engaged in the formation of a “pore” in the OMM through which pro-apoptotic factors are liberated into the cytosol (Bender and Martinou, 2013). While complexes of CLs and CLox with several OMM and intermembrane space proteins –Bcl-2 family proteins, VDAC, cyt c – have been suggested to play a role in apoptotic membrane permeabilization and pore formation (Korytowski et al, 2011; Rostovtseva and Bezrukov, 2008; Veenman et al, 2008; Xu et al, 2013), neither specific mechanisms nor physiological role of these interactions have been firmly established. Moreover, there are indications that sequestration of CLox molecules occurring without participation of any proteins may lead to the formation of pores large enough to allow for the release of pro-apoptotic factors (Jurkiewicz et al, 2012).…”
Section: Translocation and Peroxidation Of CL In Apoptosismentioning
confidence: 99%