bims-lycede Biomed News
on Lysosome-dependent cell death
Issue of 2025–06–08
two papers selected by
Sofía Peralta, Universidad Nacional de Cuyo
  1. The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance.
  2. Wet scissors: How biomolecular condensates cut cellular membranes.
  1. Autophagy Rep. 2025 ;4(1): 2476218
    The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance.
    Yingxue Wang, Matthew Jefferson, Maria Ramos, Matthew Whelband, Kristin Kreuzer, Grace Khuu, Michael Lazarou, James Mccoll, James Lazenby, Cynthia B Whitchurch, Paul Verkade, Ulrike Mayer, Thomas Wileman.
      Hydrolytic enzymes within lysosomes maintain cell and tissue homoeostasis by degrading macromolecules delivered by endocytosis and autophagy. The release of lysosomal enzymes into the cytosol can induce apoptosis and "lysosome-dependent cell death" making it important for damaged lysosomes to be repaired or removed. Extensive lysosome damage exposes luminal sugars to galectin-dependent autophagy pathways that use ATG16L1:ATG5-ATG12 complex to conjugate LC3/ATG8 to autophagosomes to facilitate removal by lysophagy. Sphingomyelin exposed on stressed lysosomes recruits the lysosome tethering protein TECPR1 (tectonin beta propeller repeat-containing protein) allowing an alternative TECRP1:ATG5-ATG12 complex to conjugate LC3 directly to lysosomes. Here we have used cells lacking ATG16L1 to follow the recruitment of TECPR1, galectin-3 and LC3/ATG8 to lysosomes in response to osmotic imbalance induced by chloroquine. TECPR1 was recruited to swollen lysosomes that exposed sphingomyelin. LC3II was absent from swollen lysosomes but located to small puncta that contained the V-ATPase and LAMP1. The presence of galectin-3 and PI4P in the small LC3 puncta suggested that the TECPR1:ATG5-ATG12 complex conjugates LC3 to lysosome remnants that have ruptured in response to osmotic imbalance.
    Keywords:  ATG16L1; Autophagy; LC3/ATG8; TECPR1; chloroquine; galectin 3; lysosome damage; osmotic stress; sphingomyelin
    DOI:  https://doi.org/10.1080/27694127.2025.2476218
  2. Curr Opin Plant Biol. 2025 Jun 03. pii: S1369-5266(25)00054-8. [Epub ahead of print]86 102740
    Wet scissors: How biomolecular condensates cut cellular membranes.
    Xiaofeng Fang, Alexander I May, Katharina Sporbeck, Lukas Hauer, Roland L Knorr.
      Membrane shape is a fundamental determinant of cellular organisation. Reshaping of membranes is crucial for dynamic processes including organelle and cell division, endocytosis and membrane trafficking. Membrane fission (or scission) is a discontinuous, topological shape change that is central in many such processes. Specialised remodelling proteins, such as dynamins and ESCRT proteins, are capable of forming oligomeric spirals that drive membrane fission in cells. In this review, we summarise evidence demonstrating that capillary forces generated by liquid-like biomolecular condensates can facilitate cellular membrane reshaping and drive fission events. We draw on our recent findings that condensates are implicated in multivesicular body formation to describe the molecular and physical principles that allow biomolecular condensates to cut membranes. We further discuss possible interactions between novel condensate-mediated fission processes and established reshaping processes. We propose that condensates make an important contribution to membrane remodelling events involved in the biogenesis of diverse cellular structures. The characterisation of condensate-mediated membrane reshaping promises to transform our understanding of intracellular organisation and dynamics.
    DOI:  https://doi.org/10.1016/j.pbi.2025.102740
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