Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37188665.
- Also identified by DOI 10.1038/s41467-023-38441-5 and PMC identifier 10185535.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IV<sub>1</sub>III<sub>2</sub>IV<sub>1</sub>) and a supercomplex (III<sub>2</sub>IV<sub>1</sub>) isolated from a cardiolipin-lacking Saccharomyces cerevisiae mutant at 3.2-Å and 3.3-Å resolution, respectively, and demonstrate that phosphatidylglycerol in III<sub>2</sub>IV<sub>1</sub> occupies similar positions as cardiolipin in IV<sub>1</sub>III<sub>2</sub>IV<sub>1</sub>. Lipid-protein interactions within these complexes differ, which conceivably underlies the reduced level of IV<sub>1</sub>III<sub>2</sub>IV<sub>1</sub> and high levels of III<sub>2</sub>IV<sub>1</sub> and free III<sub>2</sub> and IV in mutant mitochondria. Here we show that anionic phospholipids interact with positive amino acids and appear to nucleate a phospholipid domain at the interface between the individual complexes, which dampen charge repulsion and further stabilize interaction, respectively, between individual complexes.
Medical subject headings
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins