GoKawiilStudy identifies TBK1 and ULK1 as joint regulators of TFEB nuclear translocation under lysosomal stress
Researchers used TBK1-knockout cells and ULK1 knockdown to examine how cells respond to lysosomal stress induced by monensin, nigericin, salinomycin and MG132. Imaging and biochemical analyses showed that loss of TBK1 or ULK1 altered the nuclear-to-cytoplasmic distribution of the transcription factor TFEB, indicating both proteins are needed for its normal activation.
GoKawiil's interpretation of the reporting above, not reported fact.
TFEB controls genes for lysosome biogenesis and autophagy, processes implicated in neurodegeneration, cancer and metabolic disease, so mapping the signalling that activates it could reveal new drug targets. The finding that TBK1 and ULK1 act together suggests these kinases, already studied for roles in innate immunity and autophagy initiation, form a broader stress-sensing pathway than previously appreciated. Because the work relies on cell models and specific chemical stressors, it remains to be seen whether the same axis operates similarly across tissue types or in disease states.
- TBK1 and ULK1 jointly regulate TFEB's movement into the nucleus in response to lysosomal stress
- Multiple stressors (monensin, nigericin, salinomycin, MG132) and knockdown/knockout approaches were used to test the pathway
- The findings point to a signalling axis linking lysosomal stress sensing to gene expression control via TFEB
Source: nature.com — Esposito, 2026-09-30
Published there as: “A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation”
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