In-cell architecture of the mitochondrial respiratory chain, 2025, Florent Waltz et al

[Mij]

Editor’s summary
The mitochondrial respiratory chain consists of membrane-integral complexes that build up the proton gradient across the membranes of the cristae, thereby powering ATP synthase. Waltz et al. used cryo–electron tomography to resolve native structures of these complexes directly within the green alga Chlamydomonas reinhardtii.

Their findings reveal how respiratory complexes I, III, and IV assemble into a respirasome supercomplex, which is restricted to flat membrane regions apart from rows of ATP synthase at the curved tips of cristae. The work also captures fine structural details of how respirasomes are held together and how electron-carrier proteins bind these assemblies, offering insights into mitochondrial respiration inside native cells. —Stella M. Hurtley

Abstract
Mitochondria regenerate adenosine triphosphate (ATP) through oxidative phosphorylation. This process is carried out by five membrane-bound complexes collectively known as the respiratory chain, working in concert to transfer electrons and pump protons.

The precise organization of these complexes in native cells is debated. We used in situ cryo–electron tomography to visualize the native structures and organization of several major mitochondrial complexes in Chlamydomonas reinhardtii cells. ATP synthases and respiratory complexes segregate into curved and flat crista membrane domains, respectively.

Respiratory complexes I, III, and IV assemble into a respirasome supercomplex, from which we determined a native 5-angstrom (Å) resolution structure showing binding of electron carrier cytochrome c. Combined with single-particle cryo–electron microscopy at 2.4-Å resolution, we model how the respiratory complexes organize inside native mitochondria.
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[Mij]

The cell's powerhouses: Molecular machines enable efficient energy production

Perspectives into evolution and health
In the future, the researchers aim to uncover why respiratory complexes are interconnected and how this synergy enhances the efficiency of cellular respiration and energy production. The study may also offer new insights for biotechnology and health. “By examining the architecture of these complexes in other organisms, we can gain a broader understanding of their fundamental organization,” explains Waltz. “This could not only reveal evolutionary adaptations but also help us understand why disruptions in these complexes contribute to human diseases”.
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[Creekside]

Useful type of research. We need that sort of detail to figure out abnormalities. I wonder what percentage of papers citing this one will be worthwhile rather than trash.

 

[Mij]

AI overview:

Yes, cryo-electron tomography (cryo-ET) can be used to study the changes in cellular signaling pathways that occur after exercise, allowing researchers to visualize the localization of signaling molecules and the activation of signaling pathways in a near-native cellular environment.
Here's how cryo-ET can be used to study cellular signaling pathways after exercise:

• Visualization of Signaling Complexes:
  Cryo-ET enables the visualization of multimeric protein complexes, including those involved in signaling pathways, in their native cellular context. This allows researchers to observe the organization and interactions of these complexes, which can change after exercise.
• Mapping Signaling Pathway Activation:
  By analyzing the localization and organization of signaling molecules, cryo-ET can help determine which signaling pathways are activated or deactivated after exercise.
• High Resolution Imaging:
  Cryo-ET provides high-resolution 3D images of cellular structures, allowing researchers to see the fine details of signaling complexes and their interactions.
• In Situ Studies:
  Cryo-ET allows the study of cellular signaling pathways in their natural environment, without the need for purification or manipulation of samples, which can preserve the integrity of signaling molecules and their interactions.
• Correlative Microscopy:
  Cryo-ET can be combined with other microscopy techniques, such as light microscopy, to correlate structural information with functional data.

Examples of how cryo-ET has been used to study cellular signaling pathways after exercise:

• NLRP3 Inflammasome:
  Studies have used cryo-ET to visualize the ultrastructure of NLRP3 inflammasome complexes in cells, revealing their organization and how they contribute to pyroptosis.
• ASC/Caspase-1 Signalosome:
  Cryo-ET has been used to identify ASC/caspase-1 signalosome puncta and reveal their ultrastructure and pyroptotic cellular landscape in immortalized bone marrow derived macrophages.
• Exercise-Induced Signaling Pathways:
  Researchers are using cryo-ET to study the changes in signaling pathways that occur in muscle cells during and after exercise, such as the activation of AMPK (AMP-activated protein kinase).

In summary, cryo-ET is a powerful tool for studying cellular signaling pathways, providing high-resolution 3D images of signaling complexes and their interactions in a near-native cellular environment, which is invaluable for understanding how exercise affects cellular signaling and function