Radiation drives pericyte senescence through lysosome acidification failure and…

Mechanistic description

Autophagosomes still form after irradiation, but damaged lysosomes cannot clear cargo, sustaining ROS and SASP output.

Mechanism / pathway

TFEB
→
neurodegeneration

Evidence for (6)

Flux and lysosomal pH assays can sharply test a late-stage autophagy block.
Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.

PMID:39196068 2024 J Cell Biol
TFEB links autophagy to lysosomal biogenesis.

PMID:21617040 2011 Science
mTORC1-dependent TFEB nucleus translocation and pro-survival autophagy induced by zeolitic imidazolate framework-8.

PMID:32608399 2020 Biomater Sci
TFEB Signalling-Related MicroRNAs and Autophagy.

PMID:34356609 2021 Biomolecules
Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer's disease models.

PMID:38225393 2024 Acta Pharmacol Sin

Evidence against (1)

Static LC3/SQSTM1 accumulation can be misread without direct flux data.

Evidence matrix

6 supporting 1 contradicting

86% supporting

Supporting

Flux and lysosomal pH assays can sharply test a late-stage autophagy block.
Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity. PMID:39196068 · 2024 · J Cell Biol
TFEB links autophagy to lysosomal biogenesis. PMID:21617040 · 2011 · Science
mTORC1-dependent TFEB nucleus translocation and pro-survival autophagy induced by zeolitic imidazolate framework-8. PMID:32608399 · 2020 · Biomater Sci
TFEB Signalling-Related MicroRNAs and Autophagy. PMID:34356609 · 2021 · Biomolecules
Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer's disease models. PMID:38225393 · 2024 · Acta Pharmacol Sin

Contradicting

Static LC3/SQSTM1 accumulation can be misread without direct flux data.

Cite this hypothesis

Citation

etl-backfill (2026). Radiation drives pericyte senescence through lysosome acidification failure and…. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/h-780cbb9e6f

BibTeX

@misc{scidex_hypothesis_h780cbb9,
  title        = {Radiation drives pericyte senescence through lysosome acidification failure and…},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/h-780cbb9e6f},
  note         = {SciDEX artifact hypothesis:h-780cbb9e6f}
}