EMD-43055
cryo-electron tomogram of mitochondria in cryo-FIB milled s-Opa1* mouse embryonic fibroblasts
EMD-43055
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Map released: 31/01/2024
Last modified: 14/02/2024
Sample Organism:
Mus musculus
Sample: mitochondria in mouse embryonic fibroblasts with deletion of OPA1 and expression of OPA1 isoform 5
Raw data: EMPIAR-11816
Deposition Authors: Fry MY
,
Navarro PP
,
Ananda VY
,
Ge Y
,
McDonald JL
,
Hakim P
,
Lugo CM
,
Luce BE
,
Chao LH
Sample: mitochondria in mouse embryonic fibroblasts with deletion of OPA1 and expression of OPA1 isoform 5
Raw data: EMPIAR-11816
Deposition Authors: Fry MY
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In situ architecture of Opa1-dependent mitochondrial cristae remodeling.
Fry MY
,
Navarro PP
,
Hakim P
,
Ananda VY
,
Qin X
,
Landoni JC
,
Rath S,
Inde Z
,
Lugo CM
,
Luce BE
,
Ge Y
,
McDonald JL
,
Ali I,
Ha LL,
Kleinstiver BP,
Chan DC
,
Sarosiek KA
,
Chao LH
(2024) EMBO J , 43 , 391 - 413
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(2024) EMBO J , 43 , 391 - 413
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.
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.