Autophagy is best known for its role in organelle and protein turnover, cell quality control, and metabolism. The autophagic machinery has, however, also adapted to enable protein trafficking and unconventional secretory pathways so that organelles (such as autophagosomes and multivesicular bodies) delivering cargo to lysosomes for degradation can change their mission from fusion with lysosomes to fusion with the plasma membrane, followed by secretion of the cargo from the cell. Some factors with key signalling functions do not enter the conventional secretory pathway but can be secreted in an autophagy-mediated manner.Positive clinical results of some autophagy inhibitors are encouraging. Nevertheless, it is becoming clear that autophagy inhibition, even within the same cancer type, can affect cancer progression differently. Even next-generation inhibitors of autophagy can have significant non-specific effects, such as impacts on endosome-related secretory pathways and secretion of extracellular vesicles (EVs). Many studies suggest that cancer cells release higher amounts of EVs compared to non-malignant cells, which makes the effect of autophagy inhibitors on EVs secretion highly important and attractive for anticancer therapy. In this review article, we discuss how different inhibitors of autophagy may influence the secretion of EVs and summarize the non-specific effects of autophagy inhibitors with a focus on endosome-related secretory pathways. Modulation of autophagy significantly impacts not only the quantity of EVs but also their content, which can have a deep impact on the resulting pro-tumourigenic or anticancer effect of autophagy inhibitors used in the antineoplastic treatment of solid cancers.

• Klíčová slova
• Amphisomes, Autophagy, Autophagy inhibitors, Cancer, Endosomes, Exosomes, Extracellular vesicles, Multivesicular bodies, Non-conventional secretory pathways,
• MeSH
• autofagie účinky léků   MeSH
• autofagozomy metabolismus   MeSH
• cílená molekulární terapie * MeSH
• endocytóza účinky léků   MeSH
• endozomy metabolismus   MeSH
• exozómy metabolismus   MeSH
• lidé MeSH
• nádory farmakoterapie   etiologie   metabolismus   MeSH
• progrese nemoci MeSH
• proteolýza MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• sekreční dráha účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky MeSH

Endophytic fungi that colonize the plant root live in an environment with relative high concentrations of different sugars. Analyses of genome sequences indicate that such endophytes can secrete carbohydrate-related enzymes to compete for these sugars with the surrounding plant cells. We hypothesized that typical plant sugars can be used as carbon source by root endophytes and that these sugars also serve as signals to induce the expression and secretion of glycolytic enzymes. The plant-growth-promoting endophytes Serendipita indica and Serendipita herbamans were selected to first determine which sugars promote their growth and biomass formation. Secondly, particular sugars were added to liquid cultures of the fungi to induce intracellular and extracellular enzymatic activities which were measured in mycelia and culture supernatants. The results showed that both fungi cannot feed on melibiose and lactose, but instead use glucose, fructose, sucrose, mannose, arabinose, galactose and xylose as carbohydrate sources. These sugars regulated the cytoplasmic activity of glycolytic enzymes and also their secretion. The levels of induction or repression depended on the type of sugars added to the cultures and differed between the two fungi. Since no conventional signal peptide could be detected in most of the genome sequences encoding the glycolytic enzymes, a non-conventional protein secretory pathway is assumed. The results of the study suggest that root endophytic fungi translocate glycolytic activities into the root, and this process is regulated by the availability of particular plant sugars.

• Klíčová slova
• endophytic fungi, glycolysis, sugar metabolism,
• Publikační typ
• časopisecké články MeSH