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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.

Tier D because it is mechanistic or in-vitro work (model: BHD patient-derived kidney cancer cell line; Norwegian BHD patient tumor cohort), not a whole-organism health-outcome study; tier describes study design, not quality -- this is often exactly where causal biology gets established.

At a glance

Evidence tier	D Mechanistic / in vitro / review
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	2026-08-22
Source	DOI 10.1080/27694127.2026.2705631 · PMID 42569319 · Free full text (PMC13449739)

Extracted findings

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

Abstract

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. Read the full abstract on PubMed →

Cite this record

Barton, O. (2026). FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer — evidence-graded record ULL2026. In Oliver's mTOR Atlas. https://mtor-atlas.org/study/ULL2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ULL2026,
  author       = {Barton, Oliver},
  title        = {{FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer} --- evidence-graded record ULL2026},
  howpublished = {Oliver's mTOR Atlas},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ULL2026/},
  note         = {Dataset DOI: 10.5281/zenodo.22059963}
}

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