A model of mitochondrial O<sub>2</sub>consumption and ATP generation in rat proximal tubule cells
Bibliographic record
Abstract
Oxygen tension in the kidney is mostly determined by O2consumption (Qo2), which is, in turn, closely linked to tubular Na+reabsorption. The objective of the present study was to develop a model of mitochondrial function in the proximal tubule (PT) cells of the rat renal cortex to gain more insight into the coupling between Qo2, ATP formation (GATP), ATP hydrolysis (QATP), and Na+transport in the PT. The present model correctly predicts in vitro and in vivo measurements of Qo2, GATP, and ATP and Piconcentrations in PT cells. Our simulations suggest that O2levels are not rate limiting in the proximal convoluted tubule, absent large metabolic perturbations. The model predicts that the rate of ATP hydrolysis and cytoplasmic pH each substantially regulate the GATP-to-Qo2ratio, a key determinant of the number of Na+moles actively reabsorbed per mole of O2consumed. An isolated increase in QATPor in cytoplasmic pH raises the GATP-to-Qo2ratio. Thus, variations in Na+reabsorption and pH along the PT may, per se, generate axial heterogeneities in the efficiency of mitochondrial metabolism and Na+transport. Our results also indicate that the GATP-to-Qo2ratio is strongly impacted not only by H+leak permeability, which reflects mitochondrial uncoupling, but also by K+leak pathways. Simulations suggest that the negative impact of increased uncoupling in the diabetic kidney on mitochondrial metabolic efficiency is partly counterbalanced by increased rates of Na+transport and ATP consumption. This model provides a framework to investigate the role of mitochondrial dysfunction in acute and chronic renal diseases.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".