bims-nocaut Biomed News
on Non-canonical autophagy
Issue of 2026–02–15
two papers selected by
Quentin Frenger, University of Strasbourg
  1. Tributyltin induces conjugation of ATG8s to single membranes via the V-ATPase-ATG16L1 axis, leading to transcription factor EB activation in human cell lines.
  2. Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.
  1. Arch Toxicol. 2026 Feb 07.
    Tributyltin induces conjugation of ATG8s to single membranes via the V-ATPase-ATG16L1 axis, leading to transcription factor EB activation in human cell lines.
    Shunichi Hatamiya, Masatsugu Miyara, Nanako Takahashi, Ami Oguro, Yaichiro Kotake.
      Tributyltin (TBT) is an environmental contaminant that induces diverse toxic effects in mammals, but the cellular mechanisms underlying adaptation to TBT stress remain poorly understood. Conjugation of ATG8s to single membranes (CASM) is a noncanonical LC3‑lipidation pathway activated by various stressors, distinct from canonical autophagy. We previously showed that TBT reduces lysosomal acidity and inhibits autophagy in SH-SY5Y cells. Furthermore, we observed TBT-induced LC3-II accumulation, which was reduced by bafilomycin A1, and tubular LC3-positive structures as hallmarks of CASM. In this study, we investigated whether TBT activates CASM. TBT (700 nM) induced LC3-II accumulation, which was completely blocked by bafilomycin A1 in SH-SY5Y and HeLa cells. Unlike autophagy, TBT induced LC3-II accumulation even under class III PI3K inhibition by wortmannin and in FIP200-knockout cells. Salmonella effector protein SopF, which inhibits V-ATPase-ATG16L1 association required for CASM, inhibited TBT-induced LC3-II accumulation. In FIP200-knockout cells, TBT induced LC3 accumulation on lysosomes, the primary CASM target. TBT also promoted nuclear translocation of transcription factor EB (TFEB) in a SopF-sensitive manner. Together, these results identify CASM as a lysosomal stress response to TBT, induced via the V-ATPase-ATG16L1 axis, leading to TFEB activation. This mechanism provides a toxicological framework for understanding xenobiotic-induced lysosomal adaptations.
    Keywords:  CASM; LC3; Lysosome; Noncanonical autophagy; TFEB; Tributyltin
    DOI:  https://doi.org/10.1007/s00204-026-04300-7
  2. Adv Biotechnol (Singap). 2026 Feb 13. 4(1): 4
    Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.
    Rui Lin, Zhaoyuan Xu, Min Zhi.
      Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract. Autophagy, an essential intracellular homeostatic process, plays a pivotal role in the pathogenesis and progression of IBD. This review systematically examines recent advances in understanding the involvement of autophagy in IBD, with a particular focus on the regulatory mechanisms governing its sequential phases-initiation, elongation, and termination-and their respective contributions to intestinal inflammation. We highlight how dysregulation of core autophagy components, including the ULK1 complex, Beclin 1 complex, and ATG16L1, influences inflammatory responses. Furthermore, this article delves into the context-dependent roles of selective autophagy pathways such as mitophagy, ER-phagy, and xenophagy in IBD, as well as the emerging significance of non-autophagic functions exerted by autophagy-related genes. By integrating these multifaceted aspects, this review aims to provide a theoretical foundation and identify potential targets for future precision therapeutics targeting autophagy in IBD.
    Keywords:  Autophagy; Inflammatory bowel disease; Non-autophagic functions; Selective autophagy
    DOI:  https://doi.org/10.1007/s44307-026-00094-y
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