Intracellular FUS protein accumulation leads to cytoskeletal, organelle and cellular homeostasis perturbations
Bibliographic record
Abstract
Summary The molecular mechanisms that connect the formation of aberrant cytoplasmic FUS condensates to biological malfunction are incompletely understood. Here, we develop an approach to determine the intracellular FUS viscosity in live mammalian cells and find that ALS-related mutant P525L-FUS forms the most viscous condensates and has impaired cytoskeletal mechanoproperties and increased euchromatin formation. We further show that some of the main cellular organelles, e.g., actin/tubulin, lysosomes, mitochondria, the endoplasmic reticulum, are significantly functionally/structurally impaired in the presence of FUS. These may be related to defects in the tubulin network, as the latter facilitates transport, formation, fusion and fission of organelles. We observe significant increases in lysosomal biogenesis, size and pH; moreover, intracellular FUS accumulation significantly promotes cytoplasmic-to-nuclear translocation of TFEB, i.e., the master gene for inducing autophagy. However, despite these, increased autophagy needed for protein aggregate clearance is not observed to occur. Our study reveals that the formation of highly viscous FUS condensates significantly impacts cytoskeletal/organelle function and cellular homeostasis, which are closely associated with cell ageing. This raises the intriguing question as to whether mutant FUS activates similar cell processes as those during cellular senescence.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".