Oxygen-sensitive mitochondrial accumulation of cystathionine β-synthase mediated by Lon protease
Why this work is in the frame
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Bibliographic record
Abstract
Oxygen-sensitive accumulation and degradation, two opposite but intrinsically linked events, of heme proteins in mitochondria affect mitochondrial functions, including bioenergetics and oxygen-sensing processes. Cystathionine β-synthase (CBS) contains a prosthetic heme group and catalyzes the production of hydrogen sulfide in mammalian cells. Here we show that CBS proteins were present in liver mitochondria at a low level under normoxia conditions. Ischemia/hypoxia increased the accumulation of CBS proteins in mitochondria. The normalization of oxygen partial pressure accelerated the degradation of CBS proteins. Lon protease, a major degradation enzyme in mitochondrial matrix, recognized and degraded mitochondrial CBS by specifically targeting at the oxygenated heme group of CBS proteins. The accumulation of CBS in mitochondria increased hydrogen sulfide production, which prevented Ca(2+)-mediated cytochrome c release from mitochondria and decreased reactive oxygen species generation. Mitochondrial accumulation of heme oxygenase-1, another heme protein, was also regulated by oxygen level and Lon protease in the same mechanism as for CBS. Our findings provide a fundamental and general mechanism for oxygen-sensitive regulation of mitochondrial functions by linking oxygenation level to the accumulation/degradation of mitochondrial heme proteins.
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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 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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