bims-nocaut Biomed News
on Non-canonical autophagy
Issue of 2025–01–12
two papers selected by
Quentin Frenger, University of Strasbourg
  1. Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.
  2. Apoptotic breast cancer cells after chemotherapy induce pro-tumour extracellular vesicles via LAP-competent macrophages.
  1. Elife. 2025 Jan 07. pii: RP100928. [Epub ahead of print]13
    Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.
    Masroor Ahmad Paddar, Fulong Wang, Einar S Trosdal, Emily Hendrix, Yi He, Michelle R Salemi, Michal Mudd, Jingyue Jia, Thabata Duque, Ruheena Javed, Brett S Phinney, Vojo Deretic.
      ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here, we show that ATG5 associates with retromer's core components VPS26, VPS29, and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane. Knockouts of other genes essential for membrane atg8ylation, of which ATG5 is a component, affected GLUT1 sorting, indicating that membrane atg8ylation as a process affects retromer function and endosomal sorting. The contribution of membrane atg8ylation to retromer function in GLUT1 sorting was independent of canonical autophagy. These findings expand the scope of membrane atg8ylation to specific sorting processes in the cell dependent on the retromer and its known interactors.
    Keywords:  active tuberculosis; atg8ylation; autophagy; cell biology; glucose transport; human; latent tuberculosis; membrane transport; mouse
    DOI:  https://doi.org/10.7554/eLife.100928
  2. Redox Biol. 2024 Dec 28. pii: S2213-2317(24)00463-4. [Epub ahead of print]80 103485
    Apoptotic breast cancer cells after chemotherapy induce pro-tumour extracellular vesicles via LAP-competent macrophages.
    Qi Zhang, Xiaodi Liu, Qiuxia Wei, Shiyu Xiong, Wanrong Luo, Yingshi Zhou, Jincheng Cao, Xiaolin Xu, Rongbin Liu, Xinyu Tang, Wenyue Zhang, Baoming Luo.
      Chemotherapy is important in the systemic therapy for breast cancer. However, after chemotherapy, the left living tumour cells are more progressive. There is an urgent need to study the underlying mechanism which is still unclear to further improve the therapeutic efficacy of chemotherapy in breast cancer. Here we find a pro-tumour effect of the apoptotic cells induced by the chemotherapy, which is mediated by a new subset of macrophages undergoing LC3-associated phagocytosis (LAP). By transferring exosomal S100A11 into the living tumour cells after chemotherapy, the macrophage exhibits a more pro-tumour phenotype than classic M2-type macrophages. Moreover, S100A11 binds to IFITM3, inducing Akt phosphorylation of living tumour cells after chemotherapy, which promotes tumour progression. Of note, Akt inhibitor can enhance the therapeutic effcicay of chemotherapy in breast cancer. This study provides a novel mechanistic link between tumour-associated macrophages and breast cancer, uncovering Akt as a potential therapeutic target to improve chemotherapy efficacy.
    Keywords:  Breast cancer; Chemotherapy; LC3-associated phagocytosis; S100A11
    DOI:  https://doi.org/10.1016/j.redox.2024.103485
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