Open AccessCardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis
Author(s) -
Richard G. Lee,
Junjie Gao,
Stefan J. Siira,
Anne-Marie J. Shearwood,
Judith A. Ermer,
Vinzenz Hofferek,
James Mathews,
Minghao Zheng,
Gavin E. Reid,
Oliver Rackham,
Aleksandra Filipovska
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.240374
Subject(s) - cardiolipin , biology , translocase of the inner membrane , mitochondrial membrane transport protein , inner mitochondrial membrane , mitochondrial carrier , microbiology and biotechnology , translocase of the outer membrane , mitochondrion , atp–adp translocase , ribosome , endoplasmic reticulum , membrane protein , biochemistry , bacterial outer membrane , phospholipid , membrane , rna , gene , escherichia coli
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 divergent 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.