| First Author | Fry MY | Year | 2024 |
| Journal | EMBO J | Volume | 43 |
| Issue | 3 | Pages | 391-413 |
| PubMed ID | 38225406 | Mgi Jnum | J:347299 |
| Mgi Id | MGI:7622103 | Doi | 10.1038/s44318-024-00027-2 |
| Citation | Fry MY, et al. (2024) In situ architecture of Opa1-dependent mitochondrial cristae remodeling. EMBO J 43(3):391-413 |
| abstractText | 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. |
