Published in Autophagy
Resistance to chemo-immunotherapy is a major issue for the treatment of non-small cell lung cancer. In a recent paper we unravel the role of MAPK in the capacity of restraining the therapeutic efficacy of chemo-immunotherapy. Inhibition of the MAPK pathway using a MAP2K/MEK inhibitor in combination with chemotherapy could promote OPTN (optineurin)-...
Published in Autophagy
Amino acids play crucial roles in the MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) pathway. However, the underlying mechanisms are not fully understood. Here, we establish a cell-free system to mimic the activation of MTORC1, by which we identify CANX (calnexin) as an essential regulator for leucine-stimulated MTORC1 pathway. CA...
Published in Autophagy
Escherichia coli strains are responsible for a majority of human extra-intestinal infections, resulting in huge direct medical and social costs. We had previously shown that HlyF encoded by a large virulence plasmid harbored by pathogenic E. coli is not a hemolysin but a cytoplasmic enzyme leading to the overproduction of outer membrane vesicles (O...
Published in Autophagy
Two autophagy-related (ATG) ubiquitin-like conjugation systems, the ATG12 and ATG8 systems, play important roles in macroautophagy. While multiple duplications and losses of the ATG conjugation system proteins are found in different lineages, the extent to which the underlying systems diversified across eukaryotes is not fully understood. Here, in ...
Published in Autophagy
Increased bone resorption by osteoclasts after estrogen deficiency is the main cause of postmenopausal osteoporosis. TET2 (tet methylcytosine dioxygenase 2) is a DNA demethylase that regulates cellular function and differentiation potential. Macroautophagy/autophagy maintains cellular homeostasis by recycling unnecessary and damaged organelles. Thi...
Published in Autophagy
Accumulating evidence suggests that macroautophagy/autophagy dysfunction plays a critical role in myocardial ischemia-reperfusion (I/R) injury. However, the underlying mechanisms responsible for malfunctional autophagy in cardiomyocytes subjected to I/R are poorly understood. As a result, there are no effective therapeutic options that target autop...
Published in Autophagy
Mutations in the ubiquitin ligase PRKN (parkin RBR E3 ubiquitin protein ligase) are associated with Parkinson disease and defective mitophagy. Conceptually, PRKN-dependent mitophagy is classified into two phases: 1. PRKN recruits to and ubiquitinates mitochondrial proteins; 2. formation of phagophore membrane, sequestering mitochondria for degradat...
Published in Autophagy
Huntington disease is an inherited, progressive, incurable neurodegenerative disorder that primarily affects cells in the brain. Although the genetic basis for this condition has been known for nearly 30 years, how this causes disease is still unresolved. Of late there has been increasing evidence suggesting that dysfunction in macroautophagic/auto...
Published in Autophagy
Recent studies have revealed that even the nucleus can be degraded by selective macroautophagy (hereafter macronucleophagy). In Saccharomyces cerevisiae, the nuclear envelope (NE) protein Atg39 acts as a macronucleophagy receptor that mediates sequestration of nucleus-derived double-membrane vesicles (NDVs) into phagophores. The outer and inner mem...
Published in Autophagy
Inhibition of chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation for intracellular proteins, may contribute to pathogenesis in neurodegenerative diseases including Parkinson disease (PD). Pathogenic variants of PD-related proteins that reside in the cytosol, including SNCA/alpha-synuclein, LRRK2 (leucine rich repeat kinas...
