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Series GSE148178 Query DataSets for GSE148178
Status Public on Jul 08, 2020
Title Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design Total RNA was isolated, in triplicate, from NIH-3T3 cells with Crls1WT, Crls1KO1, Crls1KO2, and Crls1KO3 genotypes and TruSeq libraries prepared, sequenced and analysed for differential expression.
Contributor(s) Lee RG, Gao J, Siira SJ, SHearwood A, Ermer JA, Hofferek V, Matthews J, Zheng M, Reid G, Rackham O, Filipovska A
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Submission date Apr 06, 2020
Last update date Jul 09, 2020
Contact name Stefan J Siira
Organization name Harry Perkins Institute of Medical Research
Department Molecular medicine
Lab Mitochondrial medicine and biology
Street address 6 Verdun St, Nedlands
City Perth
State/province Western Australia
ZIP/Postal code 6009
Country Australia
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM4455688 WT_rep1
GSM4455689 WT_rep2
GSM4455690 WT_rep3
BioProject PRJNA623379
SRA SRP255456

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Supplementary file Size Download File type/resource
GSE148178_Crls1_normCounts.txt.gz 1.5 Mb (ftp)(http) TXT
GSE148178_DESeq2_results.KO1_vs_WT.txt.gz 2.0 Mb (ftp)(http) TXT
GSE148178_DESeq2_results.KO2_vs_WT.txt.gz 1.9 Mb (ftp)(http) TXT
GSE148178_DESeq2_results.KO3_vs_WT.txt.gz 1.9 Mb (ftp)(http) TXT
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Processed data are available on Series record

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