Mitochondrial dysfunction regulates the JAK–STAT pathway via LKB1-mediated AMPK activation ER-stress-independent manner
Bibliographic record
Abstract
Mitochondria affect cellular functions alone or in cooperation with other cellular organelles. Recent research has demonstrated the close relationship of mitochondria with the endoplasmic reticulum (ER), both at the physical and the functional level. In an effort to define the combined effect of mitochondrial dysfunction (MD) and ER stress in the proinflammatory activities of macrophages, the human macrophage-like monocytic leukemia cell line THP-1 was treated with mitochondrial electron transport chain (ETC) blockers, and changes in the cellular responses upon stimulation by interferon (IFN)-γ were analyzed. Inducing mitochondrial dysfunction (MD) with ETC blockers resulted in suppression of IFN-induced activation of JAK1 and STAT1/3, as well as the expression of STAT1-regulated genes. In addition, experiments utilizing pharmacological modulators of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and liver kinase B1 (LKB1)-deficient HeLa cells demonstrated that these suppressive effects are mediated by the LKB1-AMPK pathway. Treatment with pharmacological inhibitors of ER stress sensors failed to affect these processes, thus indicating that involvement of ER stress is not required. These results indicate that MD, induced by blocking the ETC, affects IFN-induced activation of JAK-STAT and associated inflammatory changes in THP-1 cells through the LKB1-AMPK pathway independently of ER stress.
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How this classification was reachedexpand
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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".