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Omics score: 1000

Cardiolipin

ABSTRACT: Cardiolipin( 1',3'-bis[1,2-dimyristoyl-sn-glycero-3-phospho]-glycerol (sodium salt)) and bovine heart cardiolipin Standards.

INSTRUMENT(S): Xevo G2-S QTOF from Waters

ORGANISM(S): Diphosphatidylglycerol Lipid

SUBMITTER: Dale Nagle

PROVIDER: MSV000083086 | MassIVE | Wed Oct 31 14:30:00 GMT 2018

REPOSITORIES: MassIVE

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GNPS - Cardiolipin

Project description:Cardiolipin( 1',3'-bis[1,2-dimyristoyl-sn-glycero-3-phospho]-glycerol (sodium salt)) and bovine heart cardiolipin Standards.

2018-10-31 | MSV000083086 | GNPS

GNPS Cardiolipin

Project description:Cardiolipin( 1',3'-bis[1,2-dimyristoyl-sn-glycero-3-phospho]-glycerol and bovine heart cardiolipin Standards.

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Genome-wide analysis of gene transcription in myocardium of mice transgenically expressing human cardiolipin synthase 1 (hCLS1) in cardiac tissue

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Cardiolipin Synthesis Governs Systemic Energy Homeostasis through Thermogenic Fat Mitochondria

Project description:Here we show that synthesis of the mitochondrial phospholipid cardiolipin is an indispensable driver of thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response by overexpressing cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency diminishes mitochondrial uncoupling in brown and beige adipocytes and elicits a nuclear transcriptional response through ER stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake and renders animals strikingly insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin is a powerful regulator of organismal energy homeostasis through thermogenic fat bioenergetics.

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Project description:The mitochondrial inner membrane contains a unique phospholipid known as cardiolipin (CL), which stabilises the protein complexes embedded in the membrane and supports its overall structure. Recent evidence indicates that the mitochondrial ribosome may associate with the inner membrane to facilitate co-translational insertion of the hydrophobic oxidative phosphorylation (OXPHOS) proteins into the inner membrane. We generated three mutant knockout cell lines for the cardiolipin biosynthesis gene Crls1 to investigate the effects of cardiolipin loss on mitochondrial protein synthesis. Reduced CL levels caused altered mitochondrial morphology and transcriptome-wide changes that were accompanied by reduced uncoordinated mitochondrial translation rates and impaired respiratory supercomplex formation. Aberrant protein synthesis was caused by impaired formation and distribution of mitochondrial ribosomes. Reduction or loss of cardiolipin resulted in resulted in different mitochondrial and endoplasmic reticulum stress responses. We show that cardiolipin is required to stabilise the interaction of the mitochondrial ribosome with the membrane via its association with OXA1 during active translation. This interaction facilitates insertion of newly synthesised mitochondrial proteins into the inner membrane and stabilises the respiratory supercomplexes.

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