In situ architecture of Opa1-dependent mitochondrial cristae remodeling
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.; Ge, Yifan; McDonald, Julie L.; Ali, Ilzat; Ha, Leillani L.; ... Show more Show less
Download44318_2024_Article_27.pdf (8.110Mb)
Publisher with Creative Commons License
Publisher with Creative Commons License
Creative Commons Attribution
Terms of use
Metadata
Show full item recordAbstract
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.
Date issued
2024-01-15Department
Massachusetts Institute of Technology. Department of BiologyJournal
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