Decision letter: Structure of a mitochondrial ATP synthase with bound native cardiolipin
Bibliographic record
Abstract
Every living thing uses the energy-rich molecule called adenosine triphosphate, or ATP, as fuel. It is the universal molecular currency for transferring energy. Cells trade it, mitochondria make it, and the energy extracted from it is used to drive chemical reactions, transport molecules across cell membranes, energize nerve impulses and contract muscles. ATP synthase is the enzyme that makes ATP molecules. It is a multi-part complex that straddles the inner membrane of mitochondria, the energy factories in cells. The enzyme complex interacts with fatty molecules in the mitochondrial inner membrane, creating a curvature that is required to produce ATP more efficiently. The mitochondrial ATP synthase has been studied in many different organisms, including yeast, algae, plants, pigs, cows and humans. These studies show that most of these ATP synthases are similar to each other, but obtaining a high resolution structure has been a challenge. Some single-cell organisms have unusual ATP synthases, which provide clues about how the enzyme evolved in pursuit of the most energy efficient arrangement. One such organism is the photosynthetic Euglena gracilis, which is closely related to the human parasites that cause sleeping sickness and Chagas disease. Now, Mü̈hleip et al. have extracted ATP synthase from E. gracilis and reconstructed its structure using electron cryo-microscopy. The high resolution of this reconstruction allowed for the first time to examine the fatty molecules associated with ATP synthase, called cardiolipins. This is important, because cardiolipins are thought to modulate the rotating motor of the enzyme and affect how the complex sits in the membrane. The analysis revealed that the ATP synthase in E. gracilis has 29 different protein subunits, 13 of which are only found in organisms of the same family. Some of the newly discovered subunits are glued together by fatty molecules and extend into the surrounding mitochondrial membrane. This distinctive structure suggests an adaptation which likely evolved independently in E. gracilis for efficiency. These results represent an important advance in the field, and provide direct evidence for the functional roles of cardiolipin. This information will be used to reconstruct the evolution of this mighty molecule and to further study the roles of cardiolipin in energy conversion. Moreover, the analysis identified similarities between the ATP synthase in E. gracilis and human parasites, which could provide new therapeutic targets in disease-causing parasites.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.114 | 0.045 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".