The Role of Cardiolipin in Mitochondrial Health and Disease

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Biochemistry and Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 7702

Special Issue Editors

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
Interests: mitochondria; mitochondrial biology; cardiolipin; genomics; mitochondrial diseases; drug development; clinical trials
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
Interests: mitochondria; mitochondrial biology; cardiolipin; genomics; mitochondrial diseases

Special Issue Information

Dear Colleagues,

Cardiolipin (CL) is a mitochondria-exclusive phospholipid that plays a pivotal role in mitochondrial architecture and function. In recent years, advances in lipidomic techniques and in vivo approaches have provided novel insights into cardiolipin metabolism and homeostasis. Moreover, aberrant CL content, structure and localisation are linked with ageing and neurodegeneration. CL has also emerged as a potential disease biomarker and pharmacological target aimed at restoring mitochondrial function. This Special Issue welcomes submissions of original research and review articles that focus on the contribution of CL to cellular homeostasis and pathophysiology. The aim is to deliver an overview of the expanding biological functions of CL and the contribution of impaired CL metabolism towards human disease states.

Dr. Robert Pitceathly
Dr. Micol Falabella
Guest Editors

Manuscript Submission Information

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Keywords

  • Mitochondria
  • Phospholipid 
  • Cardiolipin 
  • Mitochondrial diseases 
  • Bioenergetics 
  • Membrane architecture
  • Mitophagy
  • Apoptosis
  • Protein import
  • Dynamics

Published Papers (4 papers)

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14 pages, 2621 KiB  
Article
Linoleate-Enrichment of Mitochondrial Cardiolipin Molecular Species Is Developmentally Regulated and a Determinant of Metabolic Phenotype
by Genevieve C. Sparagna, Raleigh L. Jonscher, Sydney R. Shuff, Elisabeth K. Phillips, Cortney E. Wilson, Kathleen C. Woulfe, Anastacia M. Garcia, Brian L. Stauffer and Kathryn C. Chatfield
Biology 2023, 12(1), 32; https://doi.org/10.3390/biology12010032 - 24 Dec 2022
Cited by 1 | Viewed by 1712
Abstract
Cardiolipin (CL), the major mitochondrial phospholipid, regulates the activity of many mitochondrial membrane proteins. CL composition is shifted in heart failure with decreases in linoleate and increases in oleate side chains, but whether cardiolipin composition directly regulates metabolism is unknown. This study defines [...] Read more.
Cardiolipin (CL), the major mitochondrial phospholipid, regulates the activity of many mitochondrial membrane proteins. CL composition is shifted in heart failure with decreases in linoleate and increases in oleate side chains, but whether cardiolipin composition directly regulates metabolism is unknown. This study defines cardiolipin composition in rat heart and liver at three distinct ages to determine the influence of CL composition on beta-oxidation (ß-OX). CL species, expression of ß-OX and glycolytic genes, and carnitine palmitoyltransferase (CPT) activity were characterized in heart and liver from neonatal, juvenile, and adult rats. Ventricular myocytes were cultured from neonatal, juvenile, and adult rats and cardiolipin composition and CPT activity were measured. Cardiolipin composition in neonatal rat ventricular cardiomyocytes (NRVMs) was experimentally altered and mitochondrial respiration was assessed. Linoleate-enrichment of CL was observed in rat heart, but not liver, with increasing age. ß-OX genes and CPT activity were generally higher in adult heart and glycolytic genes lower, as a function of age, in contrast to liver. Palmitate oxidation increased in NRVMs when CL was enriched with linoleate. Our results indicate (1) CL is developmentally regulated, (2) linoleate-enrichment is associated with increased ß-OX and a more oxidative mitochondrial phenotype, and (3) experimentally induced linoleate-enriched CL in ventricular myocytes promotes a shift from pyruvate metabolism to fatty acid ß-OX. Full article
(This article belongs to the Special Issue The Role of Cardiolipin in Mitochondrial Health and Disease)
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14 pages, 1218 KiB  
Article
Linoleic Acid-Enriched Diet Increases Mitochondrial Tetralinoleoyl Cardiolipin, OXPHOS Protein Levels, and Uncoupling in Interscapular Brown Adipose Tissue during Diet-Induced Weight Gain
by Deena B. Snoke, Connor A. Mahler, Austin Angelotti, Rachel M. Cole, Genevieve C. Sparagna, Kedryn K. Baskin and Martha A. Belury
Biology 2023, 12(1), 9; https://doi.org/10.3390/biology12010009 - 21 Dec 2022
Cited by 5 | Viewed by 1604
Abstract
Cardiolipin (CL) is a phospholipid unique to the inner mitochondrial membrane that supports respiratory chain structure and function and is demonstrated to be influenced by types of dietary fats. However, the influence of dietary fat on CL species and how this best supports [...] Read more.
Cardiolipin (CL) is a phospholipid unique to the inner mitochondrial membrane that supports respiratory chain structure and function and is demonstrated to be influenced by types of dietary fats. However, the influence of dietary fat on CL species and how this best supports mitochondrial function in brown adipose tissue (BAT), which exhibits an alternative method of energy utilization through the uncoupling of the mitochondrial proton gradient to generate heat, is not well understood. Therefore, the aim of our study was to evaluate metabolic parameters, interscapular BAT CL quantity, species, and mitochondrial function in mice consuming isocaloric moderate-fat diets with either lard (LD; similar fatty acid profile to western dietary patterns) or safflower oil high in linoleic acid (SO), shown to be metabolically favorable in large clinical meta-analyses. Mice fed the SO diet exhibited decreased adiposity, improved insulin sensitivity, and enrichment of LA-containing CL species in BAT CL. Furthermore, mice fed the SO diet exhibit higher levels of OXPHOS complex proteins and increased oxygen consumption in BAT. Our findings demonstrate that dietary consumption of LA-rich oil improves metabolic parameters, increases LA-containing CL species, and improves BAT function when compared to the consumption of lard in mice during diet-induced weight gain. Full article
(This article belongs to the Special Issue The Role of Cardiolipin in Mitochondrial Health and Disease)
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15 pages, 3297 KiB  
Article
Ischemia In Vivo Induces Cardiolipin Oxidation in Rat Kidney Mitochondria
by Arvydas Strazdauskas, Sonata Trumbeckaite, Valdas Jakstas, Justina Kamarauskaite, Liudas Ivanauskas and Rasa Baniene
Biology 2022, 11(4), 541; https://doi.org/10.3390/biology11040541 - 31 Mar 2022
Cited by 3 | Viewed by 1703
Abstract
Cardiolipin is a mitochondrial phospholipid that plays a significant role in mitochondrial bioenergetics. Cardiolipin is oxidized under conditions like oxidative stress that occurs during ischemia/reperfusion; however, it is known that even during ischemia, many reactive oxygen species are generated. Our aim was to [...] Read more.
Cardiolipin is a mitochondrial phospholipid that plays a significant role in mitochondrial bioenergetics. Cardiolipin is oxidized under conditions like oxidative stress that occurs during ischemia/reperfusion; however, it is known that even during ischemia, many reactive oxygen species are generated. Our aim was to analyze the effect of in vivo ischemia on cardiolipin oxidation. Adult male Wistar rats were anesthetized; then, their abdomens were opened, and microvascular clips were placed on renal arteries for 30, 40 or 60 min, causing ischemia. After ischemia, kidneys were harvested, mitochondria were isolated, and lipids were extracted for chromatographic and mass spectrometric analysis of tetralinoleoyl cardiolipin and its oxidation products. Chromatographic and mass spectrometric analysis revealed a 47%, 68% and 74% decrease in tetralinoleoyl cardiolipin after 30 min, 40 min and 60 min of renal ischemia, respectively (p < 0.05). Eight different cardiolipin oxidation products with up to eight additional oxygens were identified in rat kidney mitochondria. A total of 40 min of ischemia caused an average of a 6.9-fold increase in all oxidized cardiolipin forms. We present evidence that renal ischemia in vivo alone induces tetralinoleoyl cardiolipin oxidation and depletion in rat kidney mitochondria. Full article
(This article belongs to the Special Issue The Role of Cardiolipin in Mitochondrial Health and Disease)
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9 pages, 1260 KiB  
Brief Report
Reduction in mRNA Expression of the Neutrophil Chemoattract Factor CXCL1 in Pseudomonas aeruginosa Treated Barth Syndrome B Lymphoblasts
by Hana M. Zegallai, Kangmin Duan and Grant M. Hatch
Biology 2023, 12(5), 730; https://doi.org/10.3390/biology12050730 - 16 May 2023
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Abstract
Barth Syndrome (BTHS) is a rare X-linked genetic disease caused by a mutation in the TAFAZZIN gene, which codes for the protein tafazzin involved in cardiolipin remodeling. Approximately 70% of patients with BTHS exhibit severe infections due to neutropenia. However, neutrophils from BTHS [...] Read more.
Barth Syndrome (BTHS) is a rare X-linked genetic disease caused by a mutation in the TAFAZZIN gene, which codes for the protein tafazzin involved in cardiolipin remodeling. Approximately 70% of patients with BTHS exhibit severe infections due to neutropenia. However, neutrophils from BTHS patients have been shown to exhibit normal phagocytosis and killing activity. B lymphocytes play a crucial role in the regulation of the immune system and, when activated, secrete cytokines known to attract neutrophils to sites of infection. We examined the expression of chemokine (C-X-C motif) ligand 1 (CXCL1), a known chemotactic for neutrophils, in Epstein–Barr virus transformed control and BTHS B lymphoblasts. Age-matched control and BTHS B lymphoblasts were incubated with Pseudomonas aeruginosa for 24 h and then cell viability, CD27+, CD24+, CD38+, CD138+ and PD1+ surface marker expression and CXCL1 mRNA expression determined. Cell viability was maintained in lymphoblasts incubated in a ratio of 50:1 bacteria:B cells. Surface marker expression was unaltered between control and BTHS B lymphoblasts. In contrast, CXCL1 mRNA expression was reduced approximately 70% (p < 0.05) in untreated BTHS B lymphoblasts compared to control and approximately 90% (p < 0.05) in bacterial treated BTHS B lymphoblasts compared to the control. Thus, naïve and bacterial-activated BTHS B lymphoblasts exhibit reduced mRNA expression of the neutrophil chemoattractant factor CXCL1. We suggest that impaired bacterial activation of B cells in some BTHS patients could influence neutrophil function via impairing neutrophil recruitment to sites of infection and this could potentially contribute to these infections. Full article
(This article belongs to the Special Issue The Role of Cardiolipin in Mitochondrial Health and Disease)
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