N-terminal α-amino SUMOylation promotes phosphorylation-independent cofilin-1 translocation to the mitochondrial matrix and induces apoptosis
Bibliographic record
Abstract
Cofilin is a central regulator of actin filament turnover, traditionally thought to act through phosphorylation-dependent control of filament assembly. However, its mitochondrial functions remain poorly understood. Here we show that N-terminal α-amino SUMOylation, rather than phosphorylation or actin interaction, governs cofilin-1 translocation to mitochondria and activation of the apoptotic pathway. This modification strengthens the association of cofilin-1 with the mitochondrial import receptors Tom20 and Tom70 through the molecular chaperone HSP70, enabling its delivery to the mitochondrial matrix. Once imported, SUMO-modified cofilin-1 binds cytochrome c1, promotes the dissociation of cytochrome c from complex III, and initiates mitochondrial-mediated apoptosis. These findings redefine cofilin-1 as a regulator of mitochondrial integrity independent of its actin-related roles, uncovering a mechanism by which SUMOylation directs protein targeting and apoptotic signaling. This work broadens current understanding of mitochondrial regulation and may inform therapeutic strategies for diseases linked to defective cell death. Cofilin-1 regulates cytoskeletal dynamics, but its role in mitochondria is less clear. Here, the authors demonstrate that N-terminal SUMOylation directs cofilin-1 to mitochondria, where it triggers mitochondrial dysfunction and aberrant apoptotic pathways.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".