Hryc 2023 Nat Commun

Hryc CF, Mallampalli VKPS, Bovshik EI, Azinas S, Fan G, Serysheva II, Sparagna GC, Baker ML, Mileykovskaya E, Dowhan W (2023) Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex. https://doi.org/10.1038/s41467-023-38441-5

» Nat Commun 14:2783. PMID: 37188665 Open Access

Hryc Corey F, Mallampalli Venkata KPS, Bovshik Evgeniy I, Azinas Stavros, Fan Guizhen, Serysheva Irina I, Sparagna Genevieve C, Baker Matthew L, Mileykovskaya Eugenia, Dowhan William (2023) Nat Commun

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 (IV₁III₂IV₁) and a supercomplex (III₂IV₁) isolated from a cardiolipin-lacking Saccharomyces cerevisiae mutant at 3.2-Å and 3.3-Å resolution, respectively, and demonstrate that phosphatidylglycerol in III₂IV₁ occupies similar positions as cardiolipin in IV₁III₂IV₁. Lipid-protein interactions within these complexes differ, which conceivably underlies the reduced level of IV₁III₂IV₁ and high levels of III₂IV₁ and free III₂ 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.

• Bioblast editor: Plangger M • O2k-Network Lab: US CO Aurora Sparagna GC

Labels: MiParea: Respiration, mt-Membrane 

Organism: Saccharomyces cerevisiae 

Preparation: Isolated mitochondria  Enzyme: Supercomplex 

HRR: Oxygraph-2k 

2023-06