Characterization of the impact of glutaredoxin-2 (GRX2) deficiency on superoxide/hydrogen peroxide release from cardiac and liver mitochondria
Bibliographic record
Abstract
Mitochondria are critical sources of hydrogen peroxide (H 2 O 2 ), an important secondary messenger in mammalian cells . Recent work has shown that O 2 •- /H 2 O 2 emission from individual sites of production in mitochondria is regulated by protein S-glutathionylation. Here, we conducted the first examination of O 2 •- /H 2 O 2 release rates from cardiac and liver mitochondria isolated from mice deficient for glutaredoxin-2 (GRX2), a matrix-associated thiol oxidoreductase that facilitates the S-glutathionylation and deglutathionylation of proteins. Liver mitochondria isolated from mice heterozygous (GRX2+/-) and homozygous (GRX2-/-) for glutaredoxin-2 displayed a significant decrease in O 2 •- /H 2 O 2 release when oxidizing pyruvate or 2-oxoglutarate. The genetic deletion of the Grx2 gene was associated with increased protein expression of pyruvate dehydrogenase (PDH) but not 2-oxoglutarate dehydrogenase (OGDH). By contrast, O 2 •- /H 2 O 2 production was augmented in cardiac mitochondria from GRX2+/- and GRX2-/- mice metabolizing pyruvate or 2-oxoglutarate which was associated with decreased PDH and OGDH protein levels. ROS production was augmented in liver and cardiac mitochondria metabolizing succinate . Inhibitor studies revealed that OGDH and Complex III served as high capacity ROS release sites in liver mitochondria . By contrast, Complex I and Complex III were found to be the chief O 2 •- /H 2 O 2 emitters in cardiac mitochondria. These findings identify an essential role for GRX2 in regulating O 2 •- /H 2 O 2 release from mitochondria in liver and cardiac tissue. Our results demonstrate that the GRX2-mediated regulation of O 2 •- /H 2 O 2 release through the S-glutathionylation of mitochondrial proteins may play an integral role in controlling cellular ROS signaling.
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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 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.001 |
| 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".