Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex

Author:

Hryc Corey F.,Mallampalli Venkata K. P. S.,Bovshik Evgeniy I.,Azinas StavrosORCID,Fan Guizhen,Serysheva Irina I.ORCID,Sparagna Genevieve C.,Baker Matthew L.ORCID,Mileykovskaya EugeniaORCID,Dowhan WilliamORCID

Abstract

AbstractCardiolipin 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences

John S. Dunn Research Foundation is a private foundation located in Texas

CRIPT is the CANCER PREVENTION & RESEARCH INSTITUTE OF TEXAS

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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