bims-apauto Biomed News
on Apoptosis and autophagy
Issue of 2022‒12‒04
five papers selected by
Su Hyun Lee
Seoul National University

  1. Autophagy. 2022 Nov 30.
      In this issue, we answer a frequently asked question regarding the evolution of the macroautophagy/autophagy pathway.
    Keywords:  Saccharomyces; autophagy; eukaryotes; evolution; question
  2. Autophagy. 2022 Nov 30.
      Miga is an evolutionarily conserved protein that localizes to the outer membrane of mitochondria and mediates endoplasmic reticulum (ER)-mitochondrial contacts through interaction with VAP proteins in the ER. We recently reported that Miga is required for autophagosome-lysosome fusion during macroautophagy/autophagy. Miga binds to Atg14 and Uvrag, two alternative subunits of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex. Miga regulates phosphatidylinositol-3-phosphate (PtdIns3P) levels through its interaction with Uvrag and its ER-mitochondrial contact site (ERMCS) tethering activity. Miga stabilizes Atg14, which maintains steady levels of the SNARE protein, Syx17. We propose that Miga establishes a direct link between mitochondria and autophagy to maintain cellular homeostasis.
    Keywords:  Drosophila; autophagy; endoplasmic reticulum-mitochondrial contacts; mitochondrion; phosphatidylinositol-3 kinase
  3. Autophagy. 2022 Nov 30.
    Keywords:  HLA-DM; MHC; T cells; TAX1BP1; antigen presentation; autophagy receptors; calnexin; immunopeptidome; interactome; invariant chain
  4. Front Physiol. 2022 ;13 1004330
      Acute leukemia is a common hematologic tumor with highly genetic heterogeneity, and many factors are involved in the pathogenesis and drug-resistance mechanism. Emerging evidence proves that E3 ubiquitin ligases participate in the acute leukemic signaling pathways via regulating substrates. This review summarized the E3 ligases which can affect the leukemic signal. It is worth noting that the abnormal signal is often caused by a deficiency or a mutation of the E3 ligases. In view of this phenomenon, we envisioned perspectives associated with targeted agonists of E3 ligases and proteolysis-targeting chimera technology. Moreover, we emphasized the significance of research into the upstream factors regulating the expression of E3 ubiquitin ligases. It is expected that the understanding of the mechanism of leukemic signaling pathways with which that E3 ligases are involved will be beneficial to accelerating the process of therapeutic strategy improvement for acute leukemia.
    Keywords:  E3 ubiquitin ligases; JAK2; NF-κB; Notch; PI3K/AKT; Wnt/β-catenin; acute leukemia
  5. Cell Death Differ. 2022 Nov 30.
      Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth. PML mislocalization from MAMs elicits an uncontrolled NLRP3 activation, and consequent cytokines blast fueling cancer and worsening the tumor prognosis in different human cancers. New mechanistic insights are provided for the PML-P2X7R-NLRP3 axis to govern the TME in human carcinogenesis, fostering new targeted therapeutic approaches.