The Effect of TRPML1 Inhibition by Helicobacter Pylori Vacuolating Cytotoxin on Mitochondrial Dynamics and Function
Bibliographic record
Abstract
Helicobacter pylori inhabits the stomachs of ~50% of the world’s population and is one of the leading causes of gastric cancer. H. pylori releases virulence factors, including the vacuolating cytotoxin A (VacA) which is strongly associated with disease. VacA provides H. pylori with the ability to establish chronic infection and disrupts host organelle function, particularly lysosomes and mitochondria. VacA impairs lysosomes by inhibiting transient receptor potential membrane channel 1 (TRPML1), forming non-degradative lysosomes that serve as intracellular survival niches for bacteria. Mitochondria orchestrate essential cell functions and are dependent on their ability to undergo fusion or fission, referred to as mitochondrial dynamics. Mitochondria are pivotal for regulation of lysosomal activity, as alterations in mitochondrial proteins or changes in dynamics hinder lysosome function. Conversely, defects in TRPML1, can impair mitochondrial function. The primary aim of this investigation was to determine the effect of VacA on mitochondrial dynamics and function upon long-term exposure. The results of this study show that VacA induces mitochondrial elongation after 24 hours which can be prevented with treatment of the TRPML1 agonist ML-SA1. While investigation into the mechanism behind VacA-induced mitochondrial elongation is ongoing, we have shown that it is independent of the mitochondrial fission protein dynamin-related protein 1 (Drp1) but involves altering mitochondrial fusion by increasing the ratio of long to short Optic Atrophy 1 (OPA1) isoforms. Furthermore, this study demonstrates that prolonged VacA exposure leads to mitochondrial dysfunction, evidenced by a reduction in mitochondrial transmembrane potential. Notably, ML-SA1 treatment was ineffective in preventing mitochondrial dysfunction in this context, suggesting that VacA's effects on mitochondria do not solely depend on its ability to inhibit TRPML1.
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 | 0.001 |
| 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".