ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria

Mühleip, A., Kock Flygaard, R., Ovciarikova, J., Lacombe, A., Fernandes, P., Sheiner, L. and Amunts, A. (2021) ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria. Nature Communications, 12, 120. (doi: 10.1038/s41467-020-20381-z) (PMID:33402698) (PMCID:PMC7785744)

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Abstract

Mitochondrial ATP synthase plays a key role in inducing membrane curvature to establish cristae. In Apicomplexa causing diseases such as malaria and toxoplasmosis, an unusual cristae morphology has been observed, but its structural basis is unknown. Here, we report that the apicomplexan ATP synthase assembles into cyclic hexamers, essential to shape their distinct cristae. Cryo-EM was used to determine the structure of the hexamer, which is held together by interactions between parasite-specific subunits in the lumenal region. Overall, we identified 17 apicomplexan-specific subunits, and a minimal and nuclear-encoded subunit-a. The hexamer consists of three dimers with an extensive dimer interface that includes bound cardiolipins and the inhibitor IF1. Cryo-ET and subtomogram averaging revealed that hexamers arrange into ~20-megadalton pentagonal pyramids in the curved apical membrane regions. Knockout of the linker protein ATPTG11 resulted in the loss of pentagonal pyramids with concomitant aberrantly shaped cristae. Together, this demonstrates that the unique macromolecular arrangement is critical for the maintenance of cristae morphology in Apicomplexa.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ovciarikova, Miss Jana and Sheiner, Professor Lilach and Fernandes, Ms Paula and Lacombe, Miss Alice
Authors: Mühleip, A., Kock Flygaard, R., Ovciarikova, J., Lacombe, A., Fernandes, P., Sheiner, L., and Amunts, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Nature Communications 12: 120
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172187Dissection of the unusual mitochondrial tRNA import translocon of Toxoplasma gondiiLilach SheinerBiotechnology and Biological Sciences Research Council (BBSRC)BB/N003675/1Institute of Infection, Immunity & Inflammation
307056Lost in translation. A study of the divergent mitochondrial translation pathway of the parasite Toxoplasma gondiiLilach SheinerWellcome Trust (WELLCOTR)217173/Z/19/ZMVLS - Polyomics Facility