OPA1 helical structures give perspective to mitochondrial dysfunction

Sarah B. Nyenhuis, Xufeng Wu, Marie-Paule Strub, Yang-In Yim, Abigail E. Stanton, Valentina Baena, Zulfeqhar A. Syed, Bertram Canagarajah, John A. Hammer and Jenny E. Hinshaw ()
Additional contact information
Sarah B. Nyenhuis: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Xufeng Wu: National Heart, Lung, and Blood Institute, NIH
Marie-Paule Strub: National Heart, Lung, and Blood Institute, NIH
Yang-In Yim: National Heart, Lung, and Blood Institute, NIH
Abigail E. Stanton: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Valentina Baena: National Heart, Lung, and Blood Institute, NIH
Zulfeqhar A. Syed: National Heart, Lung, and Blood Institute, NIH
Bertram Canagarajah: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
John A. Hammer: National Heart, Lung, and Blood Institute, NIH
Jenny E. Hinshaw: National Institute of Diabetes and Digestive and Kidney Diseases, NIH

Nature, 2023, vol. 620, issue 7976, 1109-1116

Abstract: Abstract Dominant optic atrophy is one of the leading causes of childhood blindness. Around 60–80% of cases1 are caused by mutations of the gene that encodes optic atrophy protein 1 (OPA1), a protein that has a key role in inner mitochondrial membrane fusion and remodelling of cristae and is crucial for the dynamic organization and regulation of mitochondria2. Mutations in OPA1 result in the dysregulation of the GTPase-mediated fusion process of the mitochondrial inner and outer membranes3. Here we used cryo-electron microscopy methods to solve helical structures of OPA1 assembled on lipid membrane tubes, in the presence and absence of nucleotide. These helical assemblies organize into densely packed protein rungs with minimal inter-rung connectivity, and exhibit nucleotide-dependent dimerization of the GTPase domains—a hallmark of the dynamin superfamily of proteins4. OPA1 also contains several unique secondary structures in the paddle domain that strengthen its membrane association, including membrane-inserting helices. The structural features identified in this study shed light on the effects of pathogenic point mutations on protein folding, inter-protein assembly and membrane interactions. Furthermore, mutations that disrupt the assembly interfaces and membrane binding of OPA1 cause mitochondrial fragmentation in cell-based assays, providing evidence of the biological relevance of these interactions.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06462-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:620:y:2023:i:7976:d:10.1038_s41586-023-06462-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06462-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().