bims-apauto 2022-12-04 papers

Issue of 2022–12–04
five papers selected by
Su Hyun Lee, Seoul National University

Autophagy. 2022 Nov 30.

The autophagy pathway beyond model organisms: an evolutionary perspective.

Sidi Zhang, Noboru Mizushima.

In this issue, we answer a frequently asked question regarding the evolution of the macroautophagy/autophagy pathway.

Keywords: Saccharomyces; autophagy; eukaryotes; evolution; question

DOI: https://doi.org/10.1080/15548627.2022.2153568

Autophagy. 2022 Nov 30.

The roles of a mitochondrial protein Miga in autophagy.

Lingna Xu, Liquan Wang, Chao Tong.

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

DOI: https://doi.org/10.1080/15548627.2022.2153569

Autophagy. 2022 Nov 30.

TAX1BP1 a novel player in antigen presentation.

Gabriela Sarango, Bénédicte Manoury, Arnaud Moris.

Keywords: HLA-DM; MHC; T cells; TAX1BP1; antigen presentation; autophagy receptors; calnexin; immunopeptidome; interactome; invariant chain

DOI: https://doi.org/10.1080/15548627.2022.2153570

Front Physiol. 2022 ;13 1004330

E3 ubiquitin ligases in the acute leukemic signaling pathways.

Qianru Zhan, Heyang Zhang, Boquan Wu, Naijin Zhang, Lijun Zhang.

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

DOI: https://doi.org/10.3389/fphys.2022.1004330

Cell Death Differ. 2022 Nov 30.

PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment.

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.

DOI: https://doi.org/10.1038/s41418-022-01095-9