Mitochondrial SUMOylation as a critical regulator of proliferation and death (349.3)
Bibliographic record
Abstract
In our search for the mechanisms that regulate mitochondrial division, we uncovered a role for SUMOylation as a post‐translational modification that regulates the activity of the fission GTPase Drp1. Although we first documented the SUMOylation of Drp1 in the activation of mitochondrial fission, there are a large number of uncharacterized SUMOylated substrates on the mitochondria. To better understand the global impact of mitochondrial SUMOylation, we identified a mitochondrial anchored SUMO E3 ligase called MAPL (mitochondrial anchored protein ligase, also called MULAN/MUL1), and SenP5, a protease that acts upon mitochondrial substrates. We previously showed that SUMOylation on the mitochondria is stabilized during cell death, and is lost during mitosis. The mitotic loss is due, at least in part, to the recruitment of SenP5 to the mitochondrial during the G2/M transition. To examine the role of mitochondrial SUMOylation in vivo, we generated a MAPL knock‐out mouse strain, which provides further evidence for a global role of mitochondrial SUMOylation in the regulation of cell survival and proliferation. These mice present with increased proliferation within the gut, resulting in a lean phenotype due to nutrient maladsorption. After 12 months, nearly 90% of the MAPL KO animals develop hepatocellular carcinoma. Combined with an analysis of the human tumor samples, our data strongly implicate MAPL as a novel mitochondrial tumor suppressor. We will discuss these data, highlighting the importance of mitochondrial SUMOylation as a critical regulator of signaling from the mitochondria.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".