Cardiolipin fatty acid remodeling regulates mitochondrial function by modifying the electron entry point in the respiratory chain

Vergeade, Aurélia; Bertram, Clinton C.; Bikineyeva, Alfiya; Zackert, William E.; Zinkel, Sandra S.; May, James M.; Dikalov, Sergey; Roberts, L. Jackson; Boutaud, Olivier

doi:10.1016/j.mito.2016.04.002

Cited by 29 publications

(22 citation statements)

References 48 publications

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“…It is essential for optimal activities of individual respiratory system complexes and supercomplexes, of ATP synthase and adenine nucleotide translocase (Paradies et al 1837). Cardiolipin content and remodeling changes the overall efficiency of the respiratory system (Vergeade et al 2016;Ye et al 2016). In our study, we observed alterations in cardiac cardiolipin fatty-acid species composition, namely a loss of the symmetric tetralinoleoyl-CL in favor of more asymmetric cardiolipins with shorter and more saturated chains (Fig.…”

Section: Discussionmentioning

confidence: 50%

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Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

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Despite the fact that skeletal muscle insulin resistance is the hallmark of type‐2 diabetes mellitus (T2DM), inflexibility in substrate energy metabolism has been observed in other tissues such as liver, adipose tissue, and heart. In the heart, structural and functional changes ultimately lead to diabetic cardiomyopathy. However, little is known about the early biochemical changes that cause cardiac metabolic dysregulation and dysfunction. We used a dietary model of fructose‐induced T2DM (10% fructose in drinking water for 6 weeks) to study cardiac fatty acid metabolism in early T2DM and related signaling events in order to better understand mechanisms of disease. In early type‐2 diabetic hearts, flux through the fatty acid oxidation pathway was increased as a result of increased cellular uptake (CD36), mitochondrial uptake (CPT1B), as well as increased β‐hydroxyacyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase activities, despite reduced mitochondrial mass. Long‐chain acyl‐CoA dehydrogenase activity was slightly decreased, resulting in the accumulation of long‐chain acylcarnitine species. Cardiac function and overall mitochondrial respiration were unaffected. However, evidence of oxidative stress and subtle changes in cardiolipin content and composition were found in early type‐2 diabetic mitochondria. Finally, we observed decreased activity of SIRT1, a pivotal regulator of fatty acid metabolism, despite increased protein levels. This indicates that the heart is no longer capable of further increasing its capacity for fatty acid oxidation. Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart.

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Section: Discussionmentioning

confidence: 50%

“…Cardiolipin content and remodeling changes the overall efficiency of the respiratory system (Vergeade et al. 2016; Ye et al. 2016).…”

Section: Discussionmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

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“…This “conical” shaped and double negatively charged CL is asymmetrically distributed in the IMM with a higher concentration of CL on the inner side of the IMM. The respiratory complexes and the adenine nucleotide carrier have an absolute requirement for CL and these complexes constitute much of the IMM protein [83-86]. With a high protein/lipid ratio ~3:1 in the IMM [87] and with CL being about ~20% of the (cardiac) mitochondrial phospholipids, the weight ratio of protein/CL phospholipids is ~15:1.…”

Section: Cardiolipin Its Molecular Structure Homo- and Hetero-acylamentioning

confidence: 99%

Known unknowns of cardiolipin signaling: The best is yet to come

Maguire

Tyurina

Mohammadyani

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

103

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Since its discovery 75 years ago, a wealth of knowledge has accumulated on the role of cardiolipin, the hallmark phospholipid of mitochondria, in bioenergetics and particularly on the structural organization of the inner mitochondrial membrane. A surge of interest in this anionic doubly-charged tetra-acylated lipid found in both prokaryotes and mitochondria has emerged based on its newly discovered signaling functions. Cardiolipin displays organ, tissue, cellular and transmembrane distribution asymmetries. A collapse of the membrane asymmetry represents a pro-mitophageal mechanism whereby externalized cardiolipin acts as an “eat-me” signal. Oxidation of cardiolipin's polyunsaturated acyl chains - catalyzed by cardiolipin complexes with cytochrome c. - is a pro-apoptotic signal. The messaging functions of myriads of cardiolipin species and their oxidation products are now being recognized as important intracellular and extracellular signals for innate and adaptive immune systems. This newly developing field of research exploring cardiolipin signaling is the main subject of this review.

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“…[4][5][6][7] Modifying the packing of the lipid can lead to structural changes and instabilities in the shape of the membrane. [1,8,9] By means of controlled environmental alterations, these changes can be investigated.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Calcium Traces in Ultrapure Water on the Lateral Organization in Tetramyristoyl Cardiolipin Monolayers

2019

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Cardiolipin (CL) plays an important role in administering the structural organization of biological membranes and therefore helps maintaining the integer membrane functionality. CL has a dimeric structure consisting of four acyl chains and two phosphate groups. With its unusual structure, the phospholipid is responsible for curvature formation in CL containing biological membranes. The acidic properties of the phosphate head groups are still not sufficiently investigated since there are controversial results in literature. The main aim of this work was to gain deeper insights into the influence of the pH on the ionization degree of CL. During the experiments, it became clear that the used ultrapure water contained traces of calcium. These unexpected calcium ions had a major impact on the behavior of CL monolayers. Therefore, the focus was put on the analysis of CL layers without and with EDTA in the subphase used to complex divalent calcium ions. For the analyses, traditional surface pressure (π) – molecular area (A) isotherm experiments combined with total reflection x‐ray fluorescence (TRXF) and grazing incidence x‐ray diffraction (GIXD) have been used.

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Cardiolipin fatty acid remodeling regulates mitochondrial function by modifying the electron entry point in the respiratory chain

Cited by 29 publications

References 48 publications

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Known unknowns of cardiolipin signaling: The best is yet to come

The Influence of Calcium Traces in Ultrapure Water on the Lateral Organization in Tetramyristoyl Cardiolipin Monolayers

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