Barth syndrome, a human disorder of cardiolipin metabolism

Schlame, Michael; Ren, Mindong

doi:10.1016/j.febslet.2006.07.022

Cited by 276 publications

(248 citation statements)

References 50 publications

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“…Mitochondria are centrally involved in neurotransmission as well as in the metabolic plasticity necessary for neuronal survival (65). Many studies have described abnormal, compromised, or enlarged mitochondria in aging, multiple neurologic diseases, and apoptosis (49,51,53,54). Aging is associated with a decreased capacity to generate ATP by oxidative phosphorylation due primarily to diminished complex I and IV activity in mitochondria (6,64,66).…”

Section: Discussionmentioning

confidence: 99%

Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Hippocampal Cardiolipin Content and Molecular Species Distribution, Mitochondrial Degeneration, Autophagy, and Cognitive Dysfunction

Mancuso

Kotzbauer

Wozniak

et al. 2009

Journal of Biological Chemistry

101

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Section: Discussionmentioning

confidence: 99%

Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Hippocampal Cardiolipin Content and Molecular Species Distribution, Mitochondrial Degeneration, Autophagy, and Cognitive Dysfunction

Mancuso

Kotzbauer

Wozniak

et al. 2009

Journal of Biological Chemistry

101

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“…27 It is essential for mitochondrial function, and dysregulation of cardiolipin induces heart failure. 28 To further confirm that mitochondrial dysfunction is the primary cause of heart failure but not secondary to the contractile dysfunction, we cultured primary cardiac myocytes isolated from RAMP2 flox/flox-αMHC-MerCreMer Tg embryos. We then induced RAMP2 deletion in vitro and proved mitochondrial dysfunction and enhanced ROS production occurred in a RAMP2 deletion-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Novel Regulation of Cardiac Metabolism and Homeostasis by the Adrenomedullin-Receptor Activity-Modifying Protein 2 System

Yoshizawa

Sakurai²,

Kamiyoshi³

et al. 2013

Hypertension

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Abstract-Adrenomedullin (AM) was identified as a vasodilating and hypotensive peptide mainly produced by the cardiovascular system. The AM receptor calcitonin receptor-like receptor associates with receptor activity-modifying protein (RAMP), one of the subtypes of regulatory proteins. Among knockout mice ( −/− ) of RAMPs, only RAMP2 −/− is embryonically lethal with cardiovascular abnormalities that are the same as AM −/− . This suggests that the AM-RAMP2 system is particularly important for the cardiovascular system. Although AM and RAMP2 are highly expressed in the heart from embryo to adulthood, their analysis has been limited by the embryonic lethality of AM −/− and RAMP2 −/−. For this study, we generated inducible cardiac myocyte-specific RAMP2 −/− (C-RAMP2). C-RAMP2 −/− exhibited dilated cardiomyopathy-like heart failure with cardiac dilatation and myofibril disruption. C-RAMP2 −/− hearts also showed changes in mitochondrial structure and downregulation of mitochondria-related genes involved in oxidative phosphorylation, β-oxidation, and reactive oxygen species regulation. Furthermore, the heart failure was preceded by changes in peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis. Metabolome and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) imaging analyses revealed early downregulation of cardiolipin, a mitochondrial membrane-specific lipid. Furthermore, primary-cultured cardiac myocytes from C-RAMP2 −/− showed reduced mitochondrial membrane potential and enhanced reactive oxygen species production in a RAMP2 deletion-dependent manner. C-RAMP2 −/− showed downregulated activation of cAMP response element binding protein (CREB), one of the main regulators of mitochondria-related genes. These data demonstrate that the AM-RAMP2 system is essential for cardiac metabolism and homeostasis. The AM-RAMP2 system is a promising therapeutic target of heart failure.

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“…The pellet was resuspended in HM buffer without BSA, and the protein concentration of the resuspended mitochondrial fractions was determined using the BCA protein assay (Thermo Scientifi c, Rockford, IL). disease states ( 12,13,(15)(16)(17)(18)(19). This diversity is regulated by differences in cardiolipin biosynthesis and catabolism, remodeling acyl selectivities, and transacylase as well as acyltransferase activities ( 20,21 ).…”

Section: Mitochondrial Isolationmentioning

confidence: 99%

Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

Kiebish

Bell

Yang

et al. 2010

Journal of Lipid Research

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Lipids are critical for the regulation and control of cellular function, membrane dynamics, and signal transduction. The systematic identifi cation and analysis of all cellular lipids in a biological sample is embodied by the rapidly developing fi eld of lipidomics, which has been enabled by recent advances in mass spectrometry ( 1-3 ). A multidimensional MS-based shotgun lipidomics (MDMS-SL) approach for analysis of cellular lipidomes has been demonstrated as one of the most systematic and quantitative high-throughput platforms for global lipidomics capable of analyzing thousands of lipid molecular species directly from the lipid extracts of biological tissues ( 4, 5 ). Analysis of lipidomic data requires extensive use of bioinformatics and computational algorithms for the accurate identifi cation and quantifi cation of lipid molecular species and classes ( 5-9 ). However, most advances in bioinformatics in lipidomics have largely focused on lipid identifi cation rather than interpretation of alterations in biological function resulting in adaptive or pathologic changes in lipid metabolism ( 10 ). Thus, development of bioinformatic and systems biology approaches for the interpretation of lipidomic networks would signifi cantly advance the understanding of the roles of lipids in biological systems ( 3 ).Cardiolipin is a complex polyglycerophospholipid found almost exclusively in mitochondrial membranes of eukaryotic organisms ( 11 ). Cardiolipin is intricately involved in the effi cient production of ATP through utilizing the proton gradient as well as maintaining mitochondrial functionality ( 12-14 ). The diversity of cardiolipin molecular species varies markedly between tissues as well as among Abstract Cardiolipin is a class of mitochondrial specifi c phospholipid, which is intricately involved in mitochondrial functionality. Differences in cardiolipin species exist in a variety of tissues and diseases. It has been demonstrated that the cardiolipin profi le is a key modulator of the functions of many mitochondrial proteins. However, the chemical mechanism(s) leading to normal and/or pathological distribution of cardiolipin species remain elusive. Herein, we describe a novel approach for investigating the molecular mechanism of cardiolipin remodeling through a dynamic simulation. This approach applied data from shotgun lipidomic analyses of the heart, liver, brain, and lung mitochondrial lipidomes to model cardiolipin remodeling, including relative content, regiospecifi city, and isomeric composition of cardiolipin species. Generated cardiolipin profi les were nearly identical to those determined by shotgun lipidomics. Importantly, the simulated isomeric compositions of cardiolipin species were further substantiated through product ion analysis. Finally, unique enzymatic activities involved in cardiolipin remodeling were assessed from the parameters used in the dynamic simulation of cardiolipin profi les. Collectively, we described, verifi ed, and demonstrated a novel approach by integrating both lipidomic ana...

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Barth syndrome, a human disorder of cardiolipin metabolism

Cited by 276 publications

References 50 publications

Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Hippocampal Cardiolipin Content and Molecular Species Distribution, Mitochondrial Degeneration, Autophagy, and Cognitive Dysfunction

Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Hippocampal Cardiolipin Content and Molecular Species Distribution, Mitochondrial Degeneration, Autophagy, and Cognitive Dysfunction

Novel Regulation of Cardiac Metabolism and Homeostasis by the Adrenomedullin-Receptor Activity-Modifying Protein 2 System

Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

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