bims-nocaut Biomed News
on Non-canonical autophagy
Issue of 2023–02–05
two papers selected by
Quentin Frenger, University of Strasbourg
  1. The participation of non-canonical autophagic proteins in the autophagy process and their potential as therapeutic targets.
  2. A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery.
  1. Expert Opin Ther Targets. 2023 Feb 03.
    The participation of non-canonical autophagic proteins in the autophagy process and their potential as therapeutic targets.
    Yiming Yin, Yourong Zhou, Xiaochun Yang, Zhifei Xu, Bo Yang, Peihua Luo, Hao Yan, Qiaojun He.
       INTRODUCTION: : Autophagy is a conserved catabolic process that help recycles intracellular component to maintain homeostasis. The completion of autophagy requires the synergistic effect of multiple canonical autophagic proteins. Defects in autophagy machinery have been reported to promote diseases, rendering autophagy a bone fide health-modifying agent. However, the clinical implication of canonical pan-autophagic activators or inhibitors has often led to undesirable side effects, making it urgent to find a safer autophagy-related therapeutic target. The discovery of the non-canonical autophagic proteins has been found to specifically affect the development of diseases without causing a universal impact on autophagy and has shed light on finding a safer way to utilize autophagy in the therapeutic context.
    AREAS COVERED: This review summarizes recently discovered non-canonical autophagic proteins, how these proteins influence autophagy, and their potential therapeutic role in the disease due to their interaction with autophagy.
    EXPERT OPINION: Several therapies have been studied thus far, and continued research is needed to identify the potential that non-canonical autophagic proteins have for treating certain diseases. In the meantime, continue to uncover new non-canonical autophagic proteins and examine which are likely to have therapeutic implications.
    Keywords:  Autophagy; Diseases; Non-canonical autophagic proteins; Therapeutic targets
    DOI:  https://doi.org/10.1080/14728222.2023.2177151
  2. Life Sci Alliance. 2023 Apr;pii: e202201715. [Epub ahead of print]6(4):
    A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery.
    Patrick Essletzbichler, Vitaly Sedlyarov, Fabian Frommelt, Didier Soulat, Leonhard X Heinz, Adrijana Stefanovic, Benedikt Neumayer, Giulio Superti-Furga.
      Phagocytosis, the process by which cells engulf large particles, plays a vital role in driving tissue clearance and host defense. Its dysregulation is connected to autoimmunity, toxic accumulation of proteins, and increased risks for infections. Despite its importance, we lack full understanding of all molecular components involved in the process. To create a functional map in human cells, we performed a genome-wide CRISPRko FACS screen that identified 716 genes. Mapping those hits to a comprehensive protein-protein interaction network annotated for functional cellular processes allowed retrieval of protein complexes identified multiple times and detection of missing phagocytosis regulators. In addition to known components, such as the Arp2/3 complex, the vacuolar-ATPase-Rag machinery, and the Wave-2 complex, we identified and validated new phagocytosis-relevant functions, including the oligosaccharyltransferase complex (MAGT1/SLC58A1, DDOST, STT3B, and RPN2) and the hypusine pathway (eIF5A, DHPS, and DOHH). Overall, our phagocytosis network comprises elements of cargo uptake, shuffling, and biotransformation through the cell, providing a resource for the identification of potential novel drivers for diseases of the endo-lysosomal system. Our approach of integrating protein-protein interaction offers a broadly applicable way to functionally interpret genome-wide screens.
    DOI:  https://doi.org/10.26508/lsa.202201715
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