bims-apauto Biomed News
on Apoptosis and autophagy
Issue of 2022‒05‒29
six papers selected by
Su Hyun Lee
Seoul National University

  1. Autophagy. 2022 May 23.
      During an animal's life, many cells undergo apoptosis, a form of genetically programmed cell death. These cells are swiftly engulfed by other cells through phagocytosis and subsequently degraded inside phagosomes. Phagocytosis and macroautophagy/autophagy are two different cellular events: whereas phagocytosis is a cell-eat-cell event, autophagy, or "self-eating", occurs within one cell, resulting in the enveloping of protein aggregates or damaged organelles within double-membrane autophagosomes. Despite this critical difference, these two events share common features: (1) both are means of safe garbage disposal; (2) both phagosomes and autophagosomes fuse to lysosomes, which drive the degradation of their contents; and (3) both events facilitate the recycling of biological materials. Previously, whether autophagosomes per se directly participate in the degradation of apoptotic cells was unknown, although autophagy proteins were implicated in apoptotic cell clearance. We recently discovered that autophagosomes fuse with phagosomes and contribute to the degradation of apoptotic cells.
    Keywords:  Autophagosomes, C. elegans; CED-1; LGG-1/LGG-2; crosstalk; degradation of apoptotic cells; membrane fusion; membrane signaling; phagocytosis; phagosomes
  2. Autophagy. 2022 May 25. 1-3
      STX17 (syntaxin 17) mediates autophagosome-lysosome fusion, and the translocation of STX17 to autophagosomes is characteristic of this process. STX17 arrives at autophagosomes when they are closed, stays there for approximately 10 min to promote fusion with lysosomes, and leaves when the autolysosomes are mature. However, the mechanism of this transient visit remains largely unknown. Here, we summarize the current knowledge about this phenomenon, including a recently discovered retrieval mechanism, and discuss remaining questions.Abbreviations: MAM: mitochondria-associated membrane; SNX: sorting nexin; STX17: syntaxin 17.
    Keywords:  ATG9; autophagosome; recycler; sorting nexin; syntaxin 17
  3. Autophagy. 2022 May 27. 1-2
      The assembly of the NLRP3 inflammasome can be initiated by a wide range of stimuli including exogenous infection as well as endogenous damage. Therefore, the tight regulation of the NLRP3 inflammasome is crucial for the host to resist microbial invasion and maintain homeostasis. Our recent work has identified a negative regulator of NLRP3-mediated inflammation, namely CCDC50 (coiled-coil domain containing protein 50). CCDC50 can be induced by NLRP3 agonists and then functions as a macroautophagy/autophagy cargo receptor to recognize K63-polyubiquitinated NLRP3 and deliver it to MAP1LC3/LC3-conjugated phagophores for degradation. CCDC50 inhibits the polymerization of NLRP3 and the recruitment of PYCARD/ASC, consequently suppressing the assembly of inflammasomes. ccdc50-knockout mice are more susceptible to dextran-sulfate (DSS)-induced colitis and exhibit more severe gut inflammation with elevated NLRP3 inflammasome activity, suggesting a protective role of CCDC50 in the pathology and progression of inflammatory bowel disease (IBD). Our finding reveals a function of autophagy-related proteins in the regulation of NLRP3-mediated inflammation, thus demonstrating the intricate crosstalk between autophagy and inflammation.
    Keywords:  Autophagy receptor; CCDC50; NLRP3 inflammasome; immune homeostasis; inflammatory bowel disease
  4. Autophagy. 2022 May 26. 1-3
      VMP1 is an ER membrane protein with phospholipid scramblase activity that has a critical role in regulating phagophore expansion and autophagosome closure. VMP1 also regulates lipid droplet formation and lipoprotein secretion in cultured cells and zebrafish. In a recent study, we showed that mice with hepatic deletion of Vmp1 have impaired very-low-density lipoprotein (VLDL) secretion and develop nonalcoholic steatohepatitis (NASH) even when fed with regular chow diet. Mechanistically, deletion of Vmp1 leads to decreased hepatic phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels as well as altered PC and PE acyl chain compositions resulting in the accumulation of neutral lipid structures in the ER phospholipid bilayer and decreased pre-VLDL assembly. These studies provide novel mechanistic insights into the non-autophagic functions of VMP1 in regulating lipoprotein secretion.
    Keywords:  ATG2; ER; TMEM41B; VLDL; VPS13D; autophagy; mitochondria
  5. Biochem J. 2022 May 27. 479(10): 1103-1119
      Apoptosis, pyroptosis, and necroptosis are distinct forms of programmed cell death that eliminate infected, damaged, or obsolete cells. Many proteins that regulate or are a part of the cell death machinery undergo ubiquitination, a post-translational modification made by ubiquitin ligases that modulates protein abundance, localization, and/or activity. For example, some ubiquitin chains target proteins for degradation, while others function as scaffolds for the assembly of signaling complexes. Deubiquitinases (DUBs) are the proteases that counteract ubiquitin ligases by cleaving ubiquitin from their protein substrates. Here, we review the DUBs that have been found to suppress or promote apoptosis, pyroptosis, or necroptosis.
    Keywords:  apoptosis; deubiquitinase; necroptosis; pyroptosis
  6. Autophagy. 2022 May 25. 1-20
      Macroautophagy/autophagy is a self-degradative process necessary for cells to maintain their energy balance during development and in response to nutrient deprivation. Autophagic processes are tightly regulated and have been found to be dysfunctional in several pathologies. Increasing experimental evidence points to the existence of an interplay between autophagy and cilia. Cilia are microtubule-based organelles protruding from the cell surface of mammalian cells that perform a variety of motile and sensory functions and, when dysfunctional, result in disorders known as ciliopathies. Indeed, selective autophagic degradation of ciliary proteins has been shown to control ciliogenesis and, conversely, cilia have been reported to control autophagy. Moreover, a growing number of players such as lysosomal and mitochondrial proteins are emerging as actors of the cilia-autophagy interplay. However, some of the published data on the cilia-autophagy axis are contradictory and indicate that we are just starting to understand the underlying molecular mechanisms. In this review, the current knowledge about this axis and challenges are discussed, as well as the implication for ciliopathies and autophagy-associated disorders.
    Keywords:  Autophagy; cilia; human diseases; lysosome; macroautophagy; mitochondria