FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer

Ullern H, Johannessen JA, Kasikci F, Formica M, Karimi Melve N, Andresen S, Brech A, Axcrona K, Jørgensen K, Farkas L, Enserink JM, Knævelsrud H · 2026 · Autophagy Reports · Atlas ID ULL2026

What this study shows

In BHD patient-derived kidney cancer cells, FLCN loss causes constitutive nuclear TFEB localization and mTORC1 hyperactivation, but leaves bulk autophagy flux and LC3 lipidation unaffected; however, the autophagy receptor SQSTM1/p62 accumulates in enlarged puncta, a finding replicated in a Norwegian cohort of BHD patient kidney tumors, showing p62 accumulation is dissociable from bulk autophagic flux.

Abstract

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Birt-Hogg-Dubé syndrome (BHD) is an autosomal, dominant condition caused by FLCN mutation and characterized by enhanced risk for kidney tumors. Previous studies have shown constitutive nuclear localization of the transcription factor TFEB and simultaneous hyperactivation of canonical MTORC1 signaling in the absence of FLCN. Here we assess the impact on autophagy under the situation of combined anabolic and catabolic activation.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: BHD patient-derived kidney cancer cell line; Norwegian BHD patient tumor cohort) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	BHD patient-derived kidney cancer cell line; Norwegian BHD patient tumor cohort
Journal	Autophagy Reports
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1080/27694127.2026.2705631 · PMID 42569319 · Free full text (PMC13449739)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	FLCN gene loss (patient-derived model; no pharmacological intervention)
Target	FLCN / mTORC1 / TFEB / SQSTM1 (p62)
Model	Human (BHD patient-derived kidney cancer cell line; Norwegian patient tumor cohort)
Effect	FLCN loss decouples SQSTM1/p62 accumulation from bulk autophagy flux despite mTORC1 hyperactivation and nuclear TFEB

In the Atlas

Cite this paper

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Ullern, H., Johannessen, J. A., Kasikci, F., Formica, M., Karimi Melve, N., Andresen, S., Brech, A., Axcrona, K., Jørgensen, K., Farkas, L., Enserink, J. M., & Knævelsrud, H. (2026). FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer. Autophagy Reports. https://doi.org/10.1080/27694127.2026.2705631

@article{ULL2026,
  author       = {Ullern, H. and Johannessen, J. A. and Kasikci, F. and Formica, M. and Karimi Melve, N. and Andresen, S. and Brech, A. and Axcrona, K. and Jørgensen, K. and Farkas, L. and Enserink, J. M. and Knævelsrud, H.},
  title        = {{FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer}},
  journal      = {Autophagy Reports},
  year         = {2026},
  doi          = {10.1080/27694127.2026.2705631},
  note         = {PMID: 42569319},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record ULL2026) [Data set]. https://mtor-atlas.org/study/ULL2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ULL2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ULL2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ULL2026/},
  doi          = {10.5281/zenodo.22059963}
}

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