Mitochondria can act as energy-sensing regulators of hydrogen peroxide availability
Bibliographic record
Abstract
Mitochondria are widely recognized as sources of reactive oxygen species in animal cells, with H 2 O 2 being of particular note because it can act not only in oxidative stress but also is important to several signalling pathways. Lesser recognized is that mitochondria can have far greater capacity to consume H 2 O 2 than to produce it; however, the consumption of H 2 O 2 may be kinetically constrained by H 2 O 2 availability especially at the low nanomolar (or lower) concentrations that occur in vivo. The production of H 2 O 2 is a function of many factors, not the least of which are respiratory substrate availability and the protonmotive force ( Δp ). The Δp , which is predominantly membrane potential ( ΔΨ ), can be a strong indicator of mitochondrial energy status, particularly if respiratory substrate supply is either not meeting or exceeding demand. The notion that mitochondria may functionally act in regulating H 2 O 2 concentrations may be somewhat implicit but little evidence demonstrating this is available. Here we demonstrate key assumptions that are required for mitochondria to act as regulators of H 2 O 2 by an integrated system of production and concomitant consumption. In particular we show the steady-state level of H 2 O 2 mitochondria approach is a function of both mitochondrial H 2 O 2 consumption and production capacity, the latter of which is strongly influenced by ΔΨ . Our results are consistent with mitochondria being able to manipulate extramitochondrial H 2 O 2 as a means of signalling mitochondrial energetic status, in particular the Δp or ΔΨ . Such a redox-based signal could operate with some independence from other energy sensing mechanisms such as those that transmit information using the cytosolic adenylate pool.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".