Defects in ordered aggregates of cardiolipin visualized by atomic force microscopy

Alessandrini, Andrea; Valdrè, Giovanni; Valdrè, U.; Muscatello, Umberto

doi:10.1016/j.chemphyslip.2007.01.001

Cited by 6 publications

(10 citation statements)

References 65 publications

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“…As a consequence of the strong amphiphilic character of cardiolipin, the polar heads of the first layer of molecules in contact with the support, are oriented toward the mica surface and interact with its charges whereas the alkyl chains are oriented almost perpendicularly to the surface. 26 The hydrophobic surface thus formed allows the formation of the cylindrical structures (inverted hexagonal phase) and its stabilization by hydrophobic interactions. The conclusion that, under the conditions used, cardiolipin molecules aggregate according to the H II phase is further supported by evidence obtained from polarized ATR-FTIR technique.…”

Section: Resultsmentioning

confidence: 99%

“…With respect to other structure determining technique AFM allows imaging in the direct space without averaging over large areas, enabling the possibility of identifying local nanoscale domains and defects. 26 However, it is worthwhile remembering that the AFM is a surface sensitive technique, so the three-dimensional structure of the sample under investigation is not always easy to deduce.…”

Section: Introductionmentioning

confidence: 99%

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AFM and FTIR Spectroscopy Investigation of the Inverted Hexagonal Phase of Cardiolipin

Alessandrini

Muscatello

2009

J. Phys. Chem. B

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Atomic force microscopy (AFM) and FTIR spectroscopy techniques have been exploited to investigate the inverted hexagonal phase (H(II)) of cardiolipin obtained by dehydration of a phospholipid water dispersion on a solid support. The characteristic cylinders of the H(II) phase have been imaged by AFM and the effects of different preparation conditions (temperature and the presence of chemicals) on the structural parameters and on the presence of local nanoscale defects have been studied. It has been found that the measured repeat spacing of the H(II) cylinders decreases upon increase of temperature and addition of pentachlorophenol (PCP), a chemical which is known to affect the structure and function of lipid bilayers. It has been shown that AFM can help in revealing some features of the mechanism of the inverted hexagonal phase formation, corroborating the results of a recent molecular dynamics study on the H(II) phase formation from multilamellar phospholipid structures.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

AFM and FTIR Spectroscopy Investigation of the Inverted Hexagonal Phase of Cardiolipin

Alessandrini

Muscatello

2009

J. Phys. Chem. B

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“…Consistent with this view, CL has been suggested to act as a proton trap by sequestering protons from the electron-transport chain via its negatively charged phospholipid head group and subsequently releasing the protons to the F 0 sector of the ATP synthase complex [44]. Another model suggests that the non-bilayer phase transition of cardiolipins in the IMM can be induced by reducing the pH [45]. Specifically, this model is supported by the observation that certain pharmacological agents that react with acidic lipids in the IMM, can inhibit both the synthesis and hydrolysis of ATP [46].…”

Section: 0 Discussionmentioning

confidence: 99%

Non-bilayer structures in mitochondrial membranes regulate ATP synthase activity

Gasanov

Kim

Yaguzhinsky

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

105

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Cardiolipin (CL) is an anionic phospholipid at the inner mitochondrial membrane (IMM) that facilitates the formation of transient non-bilayer (non-lamellar) structures to maintain mitochondrial integrity. CL modulates mitochondrial functions including ATP synthesis. However, the biophysical mechanisms by which CL generates non-lamellar structures and the extent to which these structures contribute to ATP synthesis remain unknown. We hypothesized that CL and ATP synthase facilitate the formation of non-bilayer structures at the IMM to stimulate ATP synthesis. By using H NMR andP NMR techniques, we observed that increasing the temperature (8°C to 37°C), lowering the pH (3.0), or incubating intact mitochondria with CTII - an IMM-targeted toxin that increases the formation of immobilized non-bilayer structures - elevated the formation of non-bilayer structures to stimulate ATP synthesis. The F sector of the ATP synthase complex can facilitate the formation of non-bilayer structures as incubating model membranes enriched with IMM-specific phospholipids with exogenous DCCD-binding protein of the F sector (DCCD-BPF) elevated the formation of immobilized non-bilayer structures to a similar manner as CTII. Native PAGE assays revealed that CL, but not other anionic phospholipids, specifically binds to DCCD-BPF to promote the formation of stable lipid-protein complexes. Mechanistically, molecular docking studies identified two lipid binding sites for CL in DCCD-BPF. We propose a new model of ATP synthase regulation in which CL mediates the formation of non-bilayer structures that serve to cluster protons and ATP synthase complexes as a mechanism to enhance proton translocation to the F sector, and thereby increase ATP synthesis.

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“…Multivalent counterions such as Ca 2+ have been demonstrated to be able to destabilize CL membranes, which can be stabilized again by addition of POPC. 54,55 The rich morphological behavior [4][5][6] and the sensitivity of membranes containing CLs have been suggested to have wide biological consequences, for example, in ion transport and regulation of the transmembrane voltage as well as formation of complexes particularly in mitochondria. 55,56 Complex formation, possibly mediated by ions, may be an important factor in mitochondrial apoptosis as it involves transfer of cardiolipins from the inner to the outer membrane.…”

Section: Discussionmentioning

confidence: 99%

“…3 Given these unusual features, the structure of CL is characterized by a large hydrophobic region and a strongly charged relatively small head group, which together imply that CLs favor negative curvature and form different types of aggregates ranging from cylinders to inverted micelles and hexagonal structures. [4][5][6] In biological systems, CLs are typically found in the inner bacterial and mitochondrial membranes with molar concentrations ranging from 5 to 20%. [7][8][9][10] In addition, although there are a number of different anionic lipids in typical eukaryotic cell membranes, CLs are virtually the only charged lipid species in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Role of Cardiolipins in the Inner Mitochondrial Membrane: Insight Gained through Atom-Scale Simulations

et al. 2009

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Mitochondrial membranes are unique in many ways. Unlike other cellular membranes, they are comprised of two membranes instead of just one, and cardiolipins, one of the abundant lipid species in mitochondrial membranes, are not found in significant amounts elsewhere in the cell. Among other aspects, the exceptional nature of cardiolipins is characterized by their small charged head group connected to typically four hydrocarbon chains. In this work, we present atomic-scale molecular dynamics simulations of the inner mitochondrial membrane modeled as a mixture of cardiolipins (CLs), phosphatidylcholines (PCs), and phosphatidylethanolamines (PEs). For comparison, we also consider pure one-component bilayers and mixed PC-PE, PC-CL, and PE-CL membranes. We find that the influence of CLs on membrane properties depends strongly on membrane composition. This is highlighted by studies of the stability of CL-containing membranes, which indicate that the interactions of CL in ternary lipid bilayers cannot be deduced from the corresponding ones in binary membranes. Moreover, while the membrane properties in the hydrocarbon region are only weakly affected by CLs, the changes at the membrane-water interface turn out to be prominent. The effects at the interface are most evident in membrane properties related to hydrogen bonding and the binding phenomena associated with electrostatic interactions.

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Defects in ordered aggregates of cardiolipin visualized by atomic force microscopy

Cited by 6 publications

References 65 publications

AFM and FTIR Spectroscopy Investigation of the Inverted Hexagonal Phase of Cardiolipin

AFM and FTIR Spectroscopy Investigation of the Inverted Hexagonal Phase of Cardiolipin

Non-bilayer structures in mitochondrial membranes regulate ATP synthase activity

Role of Cardiolipins in the Inner Mitochondrial Membrane: Insight Gained through Atom-Scale Simulations

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