multiple aspects of cardiolipin synthesis and ..

Cardiolipin synthesis and remodeling are tightly regulated processes ..

12/06/1996 · ↵ ‡ Heart and Stroke ..

The N-terminus of CerK bears a pleckstrin homology (PH) domain, and this domain is indispensable for its activity and acts as a regulator of its targeting and sub-cellular localization.,–) Like many PH domain-containing proteins, CerK can bind with high specificity and affinity to certain phosphatidylinositol (PI) phosphates including PI 4,5-bisphosphate (PI(4,5)P2). However, the effects of glycerophospholipids such as PI, phosphatidylcholine, and PI(4,5)P2 on CerK activity have not been well established. Cardiolipin (diphosphatidylglycerol), is a unique phospholipid with four acyl chains and two negative charges, and this lipid is generally used to measure CerK activity .,–) However, it currently remains unknown whether cardiolipin directly interacts with and activates CerK. Thus, we investigated the effects of glycerophospholipids including cardiolipin on recombinant human CerK activity in the glycerol/albumin buffer. In the present study, we showed that cardiolipin bound to CerK and regulated its activity , and that the modification of cellular cardiolipin levels changed the formation of C1P in intact cells.

21/12/2017 · Status of cardiolipin synthesis in heart ..

Cardiolipin biosynthesis and ..

In cardiac mitochondria isolated from the CLS transgenic mouse, we discovered that hyper-remodeling and increased tetra-18:2 CL content resulted in an increase in Complex III and a decrease in Complex IV activities in the CLS transgenic mouse compared with WT controls. In contrast, no differences were found in Complex I or V activities. Previously, analysis of fibroblasts from individuals with Barth syndrome, a disorder characterized by increased monolysocardiolipin content and decreased tetra-18:2 CL content, revealed a specific decrease in Complex III activity (). Thus, it is evident that regulation of tetra-18:2 CL content in cardiac mitochondria coordinately regulates the activity of Complex III, thus influencing the coupling of proton and electron donation, through Complex I and II as well as the ubiquinone cycle, respectively, thereby increasing the potential driving force of the ETC. By selectively decreasing Complex IV activity, which is allosterically inhibited by ATP content and therefore controls the efficiency of ATP generation (), the cytochrome c redox state in CLS cardiac mouse mitochondria is more efficiently coupled to the ETC, thereby utilizing less oxygen per molecule of ATP generated. Thus, selective control over specific components of the ETC complexes by CL content, molecular species composition, and lipid second messenger generation probably serves as an important regulatory mechanism underlying efficient mitochondrial bioenergetics function and signaling as well as its ability to circumvent maladaptive pathological diabetic insults ().

heart failure (HF), regulation of cardiolipin during HF development is unknown

CL from a cow heart is used as an antigen in the Wassermann test for syphilis, based on complement-fixation. A specific form of CL is found in the membrane of Treponema palladium: syphilis non-specific antibodies (RPR or reagin) react with the lipid and the intensity of the reaction (1 to 4) indicates the severity of the condition.
Anti-cardiolipin antibodies can also be increased in numerous other conditions, including systemic lupus erythematosus, malaria and tuberculosis, so this test is not specific.
The presence of antibodies to CL in plasma of patients with various diseases in which tissue damage occurs is considered to be a danger signal to the immune system. T cells responsive to CL or oxidized CL may have a function in immune surveillance during infection and tissue injury, while antibodies to CL are used in diagnostic tests after unexplained venous or arterial thrombotic episodes or recurrent miscarriages.

The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators

UCP1 Gene - GeneCards | UCP1 Protein | UCP1 Antibody

Lipidomic regulation of mitochondrial cardiolipin content and molecular species composition is a prominent regulator of bioenergetic efficiency. However, the mechanisms controlling cardiolipin metabolism during health or disease progression have remained elusive. Herein, we demonstrate that cardiac myocyte-specific transgenic expression of cardiolipin synthase results in accelerated cardiolipin lipidomic flux that impacts multiple aspects of mitochondrial bioenergetics and signaling. During the postnatal period, cardiolipin synthase transgene expression results in marked changes in the temporal maturation of cardiolipin molecular species during development. In adult myocardium, cardiolipin synthase transgene expression leads to a marked increase in symmetric tetra-18:2 molecular species without a change in total cardiolipin content. Mechanistic analysis demonstrated that these alterations result from increased cardiolipin remodeling by sequential phospholipase and transacylase/acyltransferase activities in conjunction with a decrease in phosphatidylglycerol content. Moreover, cardiolipin synthase transgene expression results in alterations in signaling metabolites, including a marked increase in the cardioprotective eicosanoid 14,15-epoxyeicosatrienoic acid. Examination of mitochondrial bioenergetic function by high resolution respirometry demonstrated that cardiolipin synthase transgene expression resulted in improved mitochondrial bioenergetic efficiency as evidenced by enhanced electron transport chain coupling using multiple substrates as well as by salutary changes in Complex III and IV activities. Furthermore, transgenic expression of cardiolipin synthase attenuated maladaptive cardiolipin remodeling and bioenergetic inefficiency in myocardium rendered diabetic by streptozotocin treatment. Collectively, these results demonstrate the unanticipated role of cardiolipin synthase in maintaining physiologic membrane structure and function even under metabolic stress, thereby identifying cardiolipin synthase as a novel therapeutic target to attenuate mitochondrial dysfunction in diabetic myocardium.