The Supramolecular Architecture of Mitochondrial Complex I in the Rat Brain Is Altered by Alzheimer's‐Like Cerebral Amyloidosis
Bibliographic record
Abstract
ABSTRACT Mitochondrial respiratory complexes are organized into supercomplexes (SC) to regulate electron flow and mitigate oxidative stress. Alterations in SC organization in the brain may affect energy expenditure, oxidative stress, and neuronal survival. In this report, we investigated the amount, activity and organization of mitochondrial complex I (CI) in the hippocampus of 12‐month‐old McGill‐R‐Thy1‐APP transgenic (Tg) rats, an animal model of Alzheimer's‐like cerebral amyloidosis. By means of BN‐PAGE, we found that the organization of SC did not differ between genotypes, but a lower abundance of SC was detected in Tg compared to wild‐type (WT) rats. Using a more sensitive technique (2‐D electrophoresis followed by Western blot), higher levels of free CI and a decrease in the relative abundance of assembled CI in SC (I‐III 2 and I‐III 2 ‐IV) were observed in Tg rats. In‐gel activity assays showed that the total activity of CI (CI + SC‐CI) is lower in Tg compared to WT, while Tg samples show a significant decrease in SC‐CI‐associated activity. This alteration in CI assembly was associated with nitro‐oxidative stress and changes in mitochondrial fusion‐fission parameters. To assess CI composition, we applied LC–MS/MS to the isolated CI from BN‐PAGE and found that 11 of 45 subunits described in mammals were found to be less abundant in Tg. We examined the levels of the nuclear‐derived NDUFA9 subunit, which is critical for CI assembly, and found higher levels in the cytoplasmic fraction and lower levels in the mitochondrial fraction in Tg, suggesting that brain amyloidosis affects the import of CI subunits from the cytosol to the mitochondria, destabilizing the SC. This is the first report to characterize the types, abundance and activity of SC in the hippocampus of an animal model of cerebral amyloidosis, providing additional experimental evidence for the molecular mechanisms underlying the brain bioenergetic deficit characteristic of Alzheimer's disease. image
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".