Characterization of the impact of glutaredoxin-2 (GRX2) deficiency on superoxide/hydrogen peroxide release from cardiac and liver mitochondria
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Bibliographic record
Abstract
Mitochondria are critical sources of hydrogen peroxide (H2O2), an important secondary messenger in mammalian cells. Recent work has shown that O2•-/H2O2 emission from individual sites of production in mitochondria is regulated by protein S-glutathionylation. Here, we conducted the first examination of O2•-/H2O2 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 O2•-/H2O2 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, O2•-/H2O2 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 O2•-/H2O2 emitters in cardiac mitochondria. These findings identify an essential role for GRX2 in regulating O2•-/H2O2 release from mitochondria in liver and cardiac tissue. Our results demonstrate that the GRX2-mediated regulation of O2•-/H2O2 release through the S-glutathionylation of mitochondrial proteins may play an integral role in controlling cellular ROS signaling.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it