In-cell architecture of the mitochondrial respiratory chain.

Summary

Using in situ cryo-electron tomography, the authors directly mapped the native structures and spatial organization of mitochondrial respiratory complexes in intact cells. These data inform how electron transport and proton pumping may be coordinated in vivo and provide a structural foundation for understanding respiratory efficiency and disease.

Key Findings

• In situ cryo-electron tomography visualized native structures and organization of major mitochondrial respiratory complexes in cells.
• The data provide direct cellular-context evidence to inform models of electron transfer and proton pumping coordination.
• Establishes a structural framework relevant to respiratory efficiency and mitochondrial disease pathophysiology.

Clinical Implications

A clear map of respiratory complex organization can guide hypotheses for mitochondrial disease mechanisms, biomarkers, and potential interventions that modulate supercomplex assembly or function.

Limitations

• Abstracted details of species, cell types, and functional validation are limited in the provided text.
• Static snapshots may not capture dynamic reorganization under varying metabolic states.

Future Directions

Integrate cryo-ET with functional assays and perturbations (e.g., metabolic stress, genetic variants) to link architecture to bioenergetic performance and disease phenotypes.