The effect of cardiolipin side chain composition on cytochrome c protein conformation and peroxidase activity

Wilkinson, Jennifer A.; Silvera, Sebastian; LeBlanc, Paul J.

doi:10.14814/phy2.14772

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…The variety of modes of interaction corresponds to a wide variety of specific reaction pathways [ 1 ]. The mechanism of interaction and the effect on heme are determined by lipid composition and pH [ 35 ]. At neutral pHs, hydrophobic interactions prevail, while at acidic pHs, cytochrome c binding is regulated by the interaction between head phosphate groups of cardiolipin and the amino acid side chains of the L-site, and NaCl has a strong influence [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Composition of the Cytochrome c Complex with Cardiolipin by Thermal Lens Spectrometry

et al. 2023

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Thermal lens spectrometry along with spectrophotometric titration were used to assess the composition of the complex of oxidized cytochrome c (ferricytochrome c) with 1,1′,2,2′-tetraoleyl cardiolipin, which plays a key role in the initiation of apoptosis. Spectrophotometric titration was carried out for micromolar concentrations at which the complex is mainly insoluble, to assess the residual concentration in the solution and to estimate the solubility of the complex. Thermal lens spectrometry was used as a method of molecular absorption spectroscopy, which has two advantages over conventional optical transmission spectroscopy: the higher sensitivity of absorbance measurements and the possibility of studying the light absorption by chromophores and heat transfer in complex systems, such as living cells or tissues. Thermal lens measurements were carried out at nanomolar concentrations, where the complex is mainly in solution, i.e., under the conditions of its direct measurements. From the thermal lens measurements, the ratios of cytochrome c and cardiolipin in the complex were 50 at pH 7.4; 30 at pH 6.8; and 10 at pH 5.5, which fit well to the spectrophotometric data. The molecular solubility of the complex at pH 6.8–7.4 was estimated as 30 µmol/L.

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Section: Discussionmentioning

confidence: 99%

Composition of the Cytochrome c Complex with Cardiolipin by Thermal Lens Spectrometry

et al. 2023

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“…Previously, we have shown in yeast mitochondria that lipid peroxidation is directly responsible for impaired electron transfer to cytochrome b in the complex III given the hydrophobic character of this subunit ( Cortés-Rojo et al, 2009 ). Moreover, the interaction of cytochrome c with cardiolipin in the presence of ROS induces cytochrome c detachment from the inner mitochondrial membrane to initiate apoptosis ( Wilkinson et al, 2021 ). Accordingly, mitochondrial ROS production was higher in the HF6, HF6+D, and HF12 groups ( Figure 7A ).…”

Section: Discussionmentioning

confidence: 99%

Avocado oil alleviates non-alcoholic fatty liver disease by improving mitochondrial function, oxidative stress and inflammation in rats fed a high fat–High fructose diet

et al. 2022

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Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in hepatocytes, and in advanced stages, by inflammation and fibrosis. Excessive ROS production due to mitochondrial dysfunction contributes to NAFLD development, making the decrease in mitochondrial ROS production an emerging target to alleviate NAFLD. Previously, we have shown that avocado oil, a source of several bioactive compounds with antioxidant effects, decreases oxidative stress by improving the function of the mitochondrial electron transport chain (ETC) and decreasing ROS levels in mitochondria of diabetic and hypertensive rats. Therefore, we tested in this work whether avocado oil alleviates NAFLD by attenuating mitochondrial dysfunction, oxidative stress and inflammation. NAFLD was induced in rats by a high fat—high fructose (HF) diet administered for six (HF6) or twelve (HF12) weeks. Hepatic steatosis, hypertrophy and inflammation were detected in both the HF6 and HF12 groups. Hyperglycemia was observed only in the HF12 group. The HF6 and HF12 groups displayed dyslipidemia, impairments in mitochondrial respiration, complex III activity, and electron transfer in cytochromes in the complex III. This led to an increase in the levels of ROS and lipid peroxidation. The substitution of the HF6 diet by standard chow and avocado oil for 6 weeks (HF6+AVO + D), or supplementation of the HF12 diet with avocado oil (HF12 + AVO), ameliorated NAFLD, hyperglycemia, dyslipidemia, and counteracted mitochondrial dysfunctions and oxidative stress. The substitution of the HF6 diet by standard chow without avocado oil did not correct many of these abnormalities, confirming that the removal of the HF diet is not enough to counteract NAFLD and mitochondrial dysfunction. In summary, avocado oil decreases NAFLD by improving mitochondrial function, oxidative stress, and inflammation.

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“…The binding of CL to cyt c induces important changes in the structure of the protein and its functional properties. Of particular interest are the changes that occur at the axial positions of the heme, as they facilitate the conversion of cyt c into a peroxidase [34][35][36][37][38]. As a peroxidase, CL-bound cyt c oxidizes the phospholipid, and the peroxidation reaction (that occurs at the initial phase of the apoptotic process) leads to the dissociation of the cyt c/CL complex [39].…”

Section: The Cytochrome C-cardiolipin Interaction Plays a Fundamental...mentioning

confidence: 99%

Cytochrome c Interaction with Cardiolipin Plays a Key Role in Cell Apoptosis: Implications for Human Diseases

et al. 2022

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In the cell cytochrome, c performs different functions depending on the environment in which it acts; therefore, it has been classified as a multifunction protein. When anchored to the outer side of the inner mitochondrial membrane, native cytochrome c acts as a Schweitzer-StennerSchweitzer-Stenner that transfers electrons from cytochrome c reductase to cytochrome c oxidase in the respiratory chain. On the other hand, to interact with cardiolipin (one of the phospholipids making up the mitochondrial membrane) and form the cytochrome c/cardiolipin complex in the apoptotic process, the protein reorganizes its structure into a non-native state characterized by different asymmetry. The formation of the cytochrome c/cardiolipin complex is a fundamental step of the apoptotic pathway, since the structural rearrangement induces peroxidase activity in cytochrome c, the subsequent permeabilization of the membrane, and the release of the free protein into the cytoplasm, where cytochrome c activates the apoptotic process. Apoptosis is closely related to the pathogenesis of neoplastic, neurodegenerative and cardiovascular diseases; in this contest, the biosynthesis and remodeling of cardiolipin are crucial for the regulation of the apoptotic process. Since the role of cytochrome c as a promoter of apoptosis strictly depends on the non-native conformation(s) that the protein acquires when bound to the cardiolipin and such event leads to cytochrome c traslocation into the cytosol, the structural and functional properties of the cytochrome c/cardiolipin complex in cell fate will be the focus of the present review.

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The effect of cardiolipin side chain composition on cytochrome c protein conformation and peroxidase activity

Cited by 8 publications

References 40 publications

Composition of the Cytochrome c Complex with Cardiolipin by Thermal Lens Spectrometry

Composition of the Cytochrome c Complex with Cardiolipin by Thermal Lens Spectrometry

Avocado oil alleviates non-alcoholic fatty liver disease by improving mitochondrial function, oxidative stress and inflammation in rats fed a high fat–High fructose diet

Cytochrome c Interaction with Cardiolipin Plays a Key Role in Cell Apoptosis: Implications for Human Diseases

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