In situ architecture of Opa1-dependent mitochondrial cristae remodeling
Name
44318_2024_Article_27.pdf
Size
8.11 MB
Format
Adobe PDF
Checksum (MD5)
cc0c61706719913bf6e73795100c327a
Author(s)
Fry, Michelle Y.
Navarro, Paula P.
Hakim, Pusparanee
Ananda, Virly Y.
Qin, Xingping
Landoni, Juan C.
Rath, Sneha
Inde, Zintis
Lugo, Camila M.
Luce, Bridget E.
Date Issued
January 15, 2024
Journal
The Embo Journal
Publisher
Nature Publishing Group UK
Citation
Fry, Michelle Y., Navarro, Paula P., Hakim, Pusparanee, Ananda, Virly Y., Qin, Xingping et al. 2024. "In situ architecture of Opa1-dependent mitochondrial cristae remodeling." The Embo Journal, 2024.
Version
Final published version
Abstract
Cristae membrane state plays a central role in regulating mitochondrial function and cellular metabolism. The protein Optic atrophy 1 (Opa1) is an important crista remodeler that exists as two forms in the mitochondrion, a membrane-anchored long form (l-Opa1) and a processed short form (s-Opa1). The mechanisms for how Opa1 influences cristae shape have remained unclear due to lack of native three-dimensional views of cristae. We perform in situ cryo-electron tomography of cryo-focused ion beam milled mouse embryonic fibroblasts with defined Opa1 states to understand how each form of Opa1 influences cristae architecture. In our tomograms, we observe a variety of cristae shapes with distinct trends dependent on s-Opa1:l-Opa1 balance. Increased l-Opa1 levels promote cristae stacking and elongated mitochondria, while increased s-Opa1 levels correlated with irregular cristae packing and round mitochondria shape. Functional assays indicate a role for l-Opa1 in wild-type apoptotic and calcium handling responses, and show a compromised respiratory function under Opa1 imbalance. In summary, we provide three-dimensional visualization of cristae architecture to reveal relationships between mitochondrial ultrastructure and cellular function dependent on Opa1-mediated membrane remodeling.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s44318-024-00027-2
