In situ architecture of Opa1-dependent mitochondrial cristae remodeling
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Nature Publishing Group UK
2024
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| Online Access: | https://hdl.handle.net/1721.1/153403 |
| _version_ | 1826217511631192064 |
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| author | 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. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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. |
| author_sort | Fry, Michelle Y. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:04:47Z |
| format | Article |
| id | mit-1721.1/153403 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:04:47Z |
| publishDate | 2024 |
| publisher | Nature Publishing Group UK |
| record_format | dspace |
| spelling | mit-1721.1/1534032024-07-11T19:58:00Z In situ architecture of Opa1-dependent mitochondrial cristae remodeling 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. Massachusetts Institute of Technology. Department of Biology 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. 2024-01-23T20:51:50Z 2024-01-23T20:51:50Z 2024-01-15 2024-01-21T04:22:22Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/153403 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. en https://doi.org/10.1038/s44318-024-00027-2 The Embo Journal Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf Nature Publishing Group UK |
| spellingShingle | 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. In situ architecture of Opa1-dependent mitochondrial cristae remodeling |
| title | In situ architecture of Opa1-dependent mitochondrial cristae remodeling |
| title_full | In situ architecture of Opa1-dependent mitochondrial cristae remodeling |
| title_fullStr | In situ architecture of Opa1-dependent mitochondrial cristae remodeling |
| title_full_unstemmed | In situ architecture of Opa1-dependent mitochondrial cristae remodeling |
| title_short | In situ architecture of Opa1-dependent mitochondrial cristae remodeling |
| title_sort | in situ architecture of opa1 dependent mitochondrial cristae remodeling |
| url | https://hdl.handle.net/1721.1/153403 |
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