Cardiolipin, the heart of mitochondrial metabolism

Houtkooper, Riekelt H.; Vaz, Frédéric M.

doi:10.1007/s00018-008-8030-5

Cited by 347 publications

(284 citation statements)

References 122 publications

Supporting

Mentioning

280

Contrasting

Order By: Relevance

“…A reduction in the amount of this labile protein suggests a defect in respiratory chain complex IV assembly. On the basis of these observations and on the fact that other studies have shown a requirement for CL in proper functioning of the respiratory chain, 38,39 we decided to investigate whether mitochondrial respiration was affected in the CLS1 KO line. To test this, cells were incubated in a medium containing galactose in which cell growth depends on functional oxidative phosphorylation.…”

Section: Resultsmentioning

confidence: 99%

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

et al. 2016

View full text Add to dashboard Cite

During apoptosis, proapoptotic BAX and BAK trigger mitochondrial outer membrane (MOM) permeabilization by a mechanism that is not yet fully understood. BH3-only proteins such as tBID, together with lipids of the MOM, are thought to play a key role in BAX and BAK activation. In particular, cardiolipin (CL) has been shown to stimulate tBID-induced BAX activation in vitro. However, it is still unclear whether this process also relies on CL in the cell, or whether it is more dependent on MTCH2, a proposed receptor for tBID present in the MOM. To address this issue, we deleted both alleles of cardiolipin synthase in human HCT116 cells by homologous recombination, which resulted in a complete absence of CL. The CL-deficient cells were fully viable in glucose but displayed impaired oxidative phosphorylation and an inability to grow in galactose. Using these cells, we found that CL was not required for either tBID-induced BAX activation, or for apoptosis in response to treatment with TRAIL. Downregulation of MTCH2 in HCT116 cells also failed to prevent recruitment of tBID to mitochondria in apoptotic conditions. However, when both CL and MTCH2 were depleted, a significant reduction in tBID recruitment was observed, suggesting that in HCT116 cells, CL and MTCH2 can have redundant functions in this process.

show abstract

Section: Resultsmentioning

confidence: 99%

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Newly synthesized cardiolipin typically undergoes remodeling to incorporate longer and more highly unsaturated acyl chains (51). Under normal conditions, CL remodeling typically is initiated by the action of a phospholipase to generate lyso-CL that is subsequently re-acylated by either transacylation or acylCoA-mediated acyltransferase activity (52). This remodeling serves to promote optimal electron transport efficiency and bioenergetic capacity in muscle where the predominant molecular species of cardiolipin is tetralinoleoyl (18:2)-CL (53).…”

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

View full text Add to dashboard Cite

show abstract

“…1 ). The newly formed polyglycerophospholipid is referred to as immature cardiolipin, which is then deacylated and extensively remodeled using acyltransferase(s) and/or transacylase(s) ( 21,22 ). Cardiolipin remodeling utilizes acyl CoA and acyl chains from the sn -2 position of choline glycerophospholipids (PC ) and ethanolamine glycerophospholipids (PE) accordingly as acyl donors ( 20,23,24 ).…”

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

View full text Add to dashboard Cite

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...

show abstract

Cardiolipin, the heart of mitochondrial metabolism

Cited by 347 publications

References 122 publications

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

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

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

Contact Info

Product

Resources

About