The physicochemical properties of cardiolipin bilayers and cardiolipin-containing lipid membranes

Lewis, Richard L.; McElhaney, Ronald N.

doi:10.1016/j.bbamem.2009.03.014

Cited by 232 publications

(200 citation statements)

References 68 publications

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“…S5) is consistent with this model, although its presence also implies that only a very small fraction of the protein ensemble is perturbed by such interactions with CL. High concentrations of salt, typically above 1.5 M for the TOCL mixtures, could also induce a nonlamellar phase formation in CL membranes (28), exposing acyl groups on the membrane surface and affecting their interactions with cyt c. However, it is not clear if these changes in CL membrane morphology play a role under our experimental conditions.…”

Section: Resultsmentioning

confidence: 48%

Conformational properties of cardiolipin-bound cytochrome c

Hanske

Toffey

Morenz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

188

388

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Interactions of cytochrome c (cyt c) with cardiolipin (CL) are important for both electron transfer and apoptotic functions of this protein. A sluggish peroxidase in its native state, when bound to CL, cyt c catalyzes CL peroxidation, which contributes to the protein apoptotic release. The heterogeneous CL-bound cyt c ensemble is difficult to characterize with traditional structural methods and ensemble-averaged probes. We have employed time-resolved FRET measurements to evaluate structural properties of the CL-bound protein in four dansyl (Dns)-labeled variants of horse heart cyt c. The Dns decay curves and extracted Dns-to-heme distance distributions PðrÞ reveal a conformational diversity of the CL-bound cyt c ensemble with distinct populations of the polypeptide structures that vary in their degree of protein unfolding. A fraction of the ensemble is substantially unfolded, with Dns-to-heme distances resembling those in the guanidine hydrochloride-denatured state. These largely open cyt c structures likely dominate the peroxidase activity of the CL-bound cyt c ensemble. Site variations in PðrÞ distributions uncover structural features of the CL-bound cyt c, rationalize previous findings, and implicate the prime role of electrostatic interactions, particularly with the protein C terminus, in the CL-induced unfolding.membrane | redox protein | fluorescence

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Section: Resultsmentioning

confidence: 48%

Conformational properties of cardiolipin-bound cytochrome c

Hanske

Toffey

Morenz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

188

388

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“…To initiate the apoptotic process the protein acquires peroxidase activity, an event which favors protein dissociation from the mitochondrial membrane [9,39,40] and the subsequent release of cyt c into the cytosol. Among the phospholipids constituting the mitochondrial membrane, CL is known to bind the hemoprotein [41]. Thus, the cyt c-CL interaction plays an important role in cells since it modulates the protein behavior determining whether cyt c should perform its 'normal' role in the respiratory chain or, conversely, is to be released into the cytosol where it participates in the apoptotic event (see [40] and references therein).…”

Section: Discussionmentioning

confidence: 99%

The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Sinibaldi¹,

Droghetti²,

Polticelli³

et al. 2011

Journal of Inorganic Biochemistry

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In cells a portion of cytochrome c (cyt c) (15-20%) is tightly bound to cardiolipin (CL), one of the phospholipids constituting the mitochondrial membrane. The CL-bound protein, which has nonnative tertiary structure, altered heme pocket, and disrupted Fe(III)-M80 axial bond, is thought to play a role in the apoptotic process. This has attracted considerable interest in order to clarify the mechanisms governing the cyt c-CL interaction. Herein we have investigated the binding reaction of CL with the c-type cytochromes from horse heart and yeast. Although the two proteins possess a similar tertiary architecture, yeast cyt c displays lower stability and, contrary to the equine protein, it does not bind ATP and lacks pro-apoptotic activity. The study has been performed in the absence and in the presence of ATP and NaCl, two compounds that influence the (horse cyt c)-CL binding process and, thus, the pro-apoptotic activity of the protein. The two proteins behave differently: while CL interaction with horse cyt c is strongly influenced by the two effectors, no effect is observed for yeast cyt c. It is noteworthy that NaCl induces dissociation of the (horse cyt c)-CL complex but has no influence on that of yeast cyt c. The differences found for the two proteins highlight that specific structural factors, such as the different local structure conformation of the regions involved in the interactions with either CL or ATP, can significantly affect the behavior of cyt c in its reaction with liposomes and the subsequent pro-apoptotic action of the protein.

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“…In contrast, free cytc participates in the electron transfer process and inhibits reactive oxygen species formation (thus preventing cell oxidative stress). Among the phospholipids constituting the mitochondrial membrane, cardiolipin (CL) is considered the preferential interacting partner with cytc; this phospholipid (which represents about 20% of total lipids of the membrane) possesses a unique structure containing four (instead of two) fatty acid tails [10].…”

Section: Introductionmentioning

confidence: 99%

Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c

Ascenzi

Ciaccio

Sinibaldi

et al. 2011

Biochemical and Biophysical Research Communications

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a b s t r a c tUpon interaction with bovine heart cardiolipin (CL), horse heart cytochrome c (cytc) changes its tertiary structure disrupting the heme-Fe-Met80 distal bond, reduces drastically the midpoint potential out of the range required for its physiological role, binds CO and NO with high affinity, and displays peroxidase activity. Here, the effect of CL on peroxynitrite isomerization by ferric cytc (cytc-Fe(III)) is reported. In the absence of CL, hexa-coordinated cytc does not catalyze peroxynitrite isomerization. In contrast, CL facilitates cytc-Fe(III)-mediated isomerization of peroxynitrite in a dose-dependent fashion inducing the penta-coordination of the heme-Fe(III)-atom. The value of the second order rate constant for CLcytc-Fe(III)-mediated isomerization of peroxynitrite (k on ) is (3.2 ± 0.4) Â 10 5 M À1 s À1. The apparent dissociation equilibrium constant for CL binding to cytc-Fe(III) is (5.1 ± 0.8) Â 10 À5 M. These results suggest that CL-cytc could play either pro-apoptotic or anti-apoptotic effects facilitating lipid peroxidation and scavenging of reactive nitrogen species, such as peroxynitrite, respectively.

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The physicochemical properties of cardiolipin bilayers and cardiolipin-containing lipid membranes

Cited by 232 publications

References 68 publications

Conformational properties of cardiolipin-bound cytochrome c

Conformational properties of cardiolipin-bound cytochrome c

The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c

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