Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Language: | English |
| Published: |
COMPANY BIOLOGISTS LTD
2020
|
| Subjects: | |
| Online Access: | http://purl.org/au-research/grants/arc/DP180101656 http://hdl.handle.net/20.500.11937/90864 |
| _version_ | 1848765445093457920 |
|---|---|
| author | Lee, R.G. Gao, J. Siira, S.J. Shearwood, A.M. Ermer, J.A. Hofferek, V. Mathews, J.C. Zheng, M. Reid, G.E. Rackham, Oliver Filipovska, Aleksandra |
| author_facet | Lee, R.G. Gao, J. Siira, S.J. Shearwood, A.M. Ermer, J.A. Hofferek, V. Mathews, J.C. Zheng, M. Reid, G.E. Rackham, Oliver Filipovska, Aleksandra |
| author_sort | Lee, R.G. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| 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 CL biosynthesis gene Crls1 to investigate the effects of CL loss on mitochondrial protein synthesis. Reduced CL levels caused altered mitochondrial morphology and transcriptome-wide changes that were accompanied by uncoordinated mitochondrial translation rates and impaired respiratory chain supercomplex formation. Aberrant protein synthesis was caused by impaired formation and distribution of mitochondrial ribosomes. Reduction or loss of CL resulted in divergent mitochondrial and endoplasmic reticulum stress responses. We show that CL is required to stabilise the interaction of the mitochondrial ribosome with the membrane via its association with OXA1 (also known as OXA1L) during active translation. This interaction facilitates insertion of newly synthesised mitochondrial proteins into the inner membrane and stabilises the respiratory supercomplexes. |
| first_indexed | 2025-11-14T11:35:21Z |
| format | Journal Article |
| id | curtin-20.500.11937-90864 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:35:21Z |
| publishDate | 2020 |
| publisher | COMPANY BIOLOGISTS LTD |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-908642023-05-05T06:04:34Z Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis Lee, R.G. Gao, J. Siira, S.J. Shearwood, A.M. Ermer, J.A. Hofferek, V. Mathews, J.C. Zheng, M. Reid, G.E. Rackham, Oliver Filipovska, Aleksandra Science & Technology Life Sciences & Biomedicine Cell Biology Mitochondrial membrane Protein synthesis Mitochondrial ribosomes Cardiolipin C-TERMINAL TAIL RNA GRANULES QUANTIFICATION IDENTIFICATION DYSFUNCTION SUBUNIT COMPLEX CRISTAE STRESS Cardiolipin Mitochondrial membrane Mitochondrial ribosomes Protein synthesis Cardiolipins Mitochondria Mitochondrial Membranes Mitochondrial Proteins Mitochondrial Ribosomes Mitochondria Cardiolipins Mitochondrial Proteins Mitochondrial Membranes Mitochondrial Ribosomes 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 CL biosynthesis gene Crls1 to investigate the effects of CL loss on mitochondrial protein synthesis. Reduced CL levels caused altered mitochondrial morphology and transcriptome-wide changes that were accompanied by uncoordinated mitochondrial translation rates and impaired respiratory chain supercomplex formation. Aberrant protein synthesis was caused by impaired formation and distribution of mitochondrial ribosomes. Reduction or loss of CL resulted in divergent mitochondrial and endoplasmic reticulum stress responses. We show that CL is required to stabilise the interaction of the mitochondrial ribosome with the membrane via its association with OXA1 (also known as OXA1L) during active translation. This interaction facilitates insertion of newly synthesised mitochondrial proteins into the inner membrane and stabilises the respiratory supercomplexes. 2020 Journal Article http://hdl.handle.net/20.500.11937/90864 10.1242/jcs.240374 English http://purl.org/au-research/grants/arc/DP180101656 COMPANY BIOLOGISTS LTD fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Cell Biology Mitochondrial membrane Protein synthesis Mitochondrial ribosomes Cardiolipin C-TERMINAL TAIL RNA GRANULES QUANTIFICATION IDENTIFICATION DYSFUNCTION SUBUNIT COMPLEX CRISTAE STRESS Cardiolipin Mitochondrial membrane Mitochondrial ribosomes Protein synthesis Cardiolipins Mitochondria Mitochondrial Membranes Mitochondrial Proteins Mitochondrial Ribosomes Mitochondria Cardiolipins Mitochondrial Proteins Mitochondrial Membranes Mitochondrial Ribosomes Lee, R.G. Gao, J. Siira, S.J. Shearwood, A.M. Ermer, J.A. Hofferek, V. Mathews, J.C. Zheng, M. Reid, G.E. Rackham, Oliver Filipovska, Aleksandra Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis |
| title | Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis |
| title_full | Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis |
| title_fullStr | Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis |
| title_full_unstemmed | Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis |
| title_short | Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis |
| title_sort | cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis |
| topic | Science & Technology Life Sciences & Biomedicine Cell Biology Mitochondrial membrane Protein synthesis Mitochondrial ribosomes Cardiolipin C-TERMINAL TAIL RNA GRANULES QUANTIFICATION IDENTIFICATION DYSFUNCTION SUBUNIT COMPLEX CRISTAE STRESS Cardiolipin Mitochondrial membrane Mitochondrial ribosomes Protein synthesis Cardiolipins Mitochondria Mitochondrial Membranes Mitochondrial Proteins Mitochondrial Ribosomes Mitochondria Cardiolipins Mitochondrial Proteins Mitochondrial Membranes Mitochondrial Ribosomes |
| url | http://purl.org/au-research/grants/arc/DP180101656 http://hdl.handle.net/20.500.11937/90864 |