- Email: [email protected]
Autophagy deficient mice as a model for studying stress-induced autophagy in vivo
S20
M. Casal / Free Radical Biology and Medicine 120 (2018) S6–S23
aggregated proteins and damaged or superfluous organelles. Given that autophagy is broadly involved in many key aspects of cellular homeostasis, it is not surprising that its dysfunction attributes to various human diseases, among them neurodegenerative diseases and cancer. The biogenesis of autophagosomes starts from a poorly characterized initial membrane structure, the phagophore, and proceeds through phagophore expansion, i.e. the growth of autophagosomal membranes, by an equally undefined mechanism. We study the connection of the endoplasmic reticulum (ER) to autophagosome biogenesis during starvation using yeast as model organism. We will present recent data and provide a model for how specific vesicular traffic from the ER provides membranes to autophagosomes.
E-mail address: [email protected]
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.082
L-54
Free radicals at the crossroads of autophagy and immunity
As a stress-induced mechanism, autophagy provides energy and essential biomolecules through degradation of cellular cytoplasmic constituents, thus helping cells to adapt to nutrient scarcity. Autophagy regulation by nutrient availability has been evolutionarily conserved from the simplest eukaryotic organisms, as yeasts, to mammals or plants. Apart from this ancient energy-providing role, autophagy has evolved to act as a basal, constitutively-activated, catabolic route preventing accumulation of detrimental intracellular structures, thus keeping cells homeostasis and organism integrity. To better understand autophagy's roles in higher eukaryotes, a variety of autophagy-deficient mice have currently been generated. The study of these modes has provided clues on how basal autophagy sustains cellular health, tissue-specific functions and organismal response to environmental factors. We will describe how the study of autophagy-deficient animal models has improved our understanding on how this catabolic route protects cells, tissues and organisms either as a constitutive or inducible pathway. Finally, we will discuss the differences between animal models with either total or partial autophagy inactivation and explain the advantages for each of these complementary strategies.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.084
Jennifer Martinez NIEHS, Research Triangle Park, NC, USA
L-56
The role of autophagy and cancer We now recognize that the autophagy machinery functions in a multitude of non-canonical biological pathways, including the host defense to extracellular threats, such as pathogens. We have identified a form of non-canonical autophagy termed LC3-associated phagocytosis (LAP), wherein phagosomes containing engulfed particles, including pathogens and dying cells, recruit elements of the autophagy pathway to facilitate phagosome maturation, digestion of cargo, and modulation of innate immunity. We have characterized Rubicon as a LAP-specific, autophagy-independent molecule, allowing the study of the unique role of LAP. To better understand host factors that may play a role in infection, we investigated the role of Rubicon during Salmonella enterica Typhimurium infection. Macrophages lacking Rubicon failed to control S. enterica Typhimurium and produced a markedly decreased ability to produce free radicals during infection compared to wild type macrophages. Rubicondeficient cells also displayed a hyperactivation of canonical Nf-Kb signaling, demonstrating a failure to coordinate an appropriate inflammatory reaction. Rubicon-/mice demonstrate that Rubicon is essential for several aspects of pathology including replication control and immunological response.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.083
L-55
Autophagy deficient mice as a model for studying stress-induced autophagy in vivo Guillermo Mariño University of Oviedo / Principality of Asturias Sanitary Research Institute (ISPA), Oviedo, Spain
Guillermo Velasco Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain
Autophagy is the main cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles and represents the principle catabolic process regulating cellular homeostasis and organelle and protein turnover. Besides its role in cellular homeostasis, autophagy can be a form of programmed cell death or play a cytoprotective role, for example in situations of nutrient starvation. Accordingly, autophagy plays a dual role in cancer as this cellular process may help to overcome the stress evoked at the initial steps of tumorigenesis or work as a tumor suppressor mechanism. Moreover, different anticancer treatments activate autophagy in tumor cells, which either enhance cancer cell death or act as a mechanism of resistance to chemotherapy. Prior work by our group showed that Δ9-tetrahydrocannabinol (THC, the main active component of marijuana) triggers autophagy-mediated cancer cell death. In this presentation I will summarize several recent findings supporting that the modification of the sphingolipid metabolism of cancer cells by cannabinoids plays a pivotal role in the stimulation of autophagy-mediated cancer cell death.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.085
M. Casal / Free Radical Biology and Medicine 120 (2018) S6–S23
aggregated proteins and damaged or superfluous organelles. Given that autophagy is broadly involved in many key aspects of cellular homeostasis, it is not surprising that its dysfunction attributes to various human diseases, among them neurodegenerative diseases and cancer. The biogenesis of autophagosomes starts from a poorly characterized initial membrane structure, the phagophore, and proceeds through phagophore expansion, i.e. the growth of autophagosomal membranes, by an equally undefined mechanism. We study the connection of the endoplasmic reticulum (ER) to autophagosome biogenesis during starvation using yeast as model organism. We will present recent data and provide a model for how specific vesicular traffic from the ER provides membranes to autophagosomes.
E-mail address: [email protected]
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.082
L-54
Free radicals at the crossroads of autophagy and immunity
As a stress-induced mechanism, autophagy provides energy and essential biomolecules through degradation of cellular cytoplasmic constituents, thus helping cells to adapt to nutrient scarcity. Autophagy regulation by nutrient availability has been evolutionarily conserved from the simplest eukaryotic organisms, as yeasts, to mammals or plants. Apart from this ancient energy-providing role, autophagy has evolved to act as a basal, constitutively-activated, catabolic route preventing accumulation of detrimental intracellular structures, thus keeping cells homeostasis and organism integrity. To better understand autophagy's roles in higher eukaryotes, a variety of autophagy-deficient mice have currently been generated. The study of these modes has provided clues on how basal autophagy sustains cellular health, tissue-specific functions and organismal response to environmental factors. We will describe how the study of autophagy-deficient animal models has improved our understanding on how this catabolic route protects cells, tissues and organisms either as a constitutive or inducible pathway. Finally, we will discuss the differences between animal models with either total or partial autophagy inactivation and explain the advantages for each of these complementary strategies.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.084
Jennifer Martinez NIEHS, Research Triangle Park, NC, USA
L-56
The role of autophagy and cancer We now recognize that the autophagy machinery functions in a multitude of non-canonical biological pathways, including the host defense to extracellular threats, such as pathogens. We have identified a form of non-canonical autophagy termed LC3-associated phagocytosis (LAP), wherein phagosomes containing engulfed particles, including pathogens and dying cells, recruit elements of the autophagy pathway to facilitate phagosome maturation, digestion of cargo, and modulation of innate immunity. We have characterized Rubicon as a LAP-specific, autophagy-independent molecule, allowing the study of the unique role of LAP. To better understand host factors that may play a role in infection, we investigated the role of Rubicon during Salmonella enterica Typhimurium infection. Macrophages lacking Rubicon failed to control S. enterica Typhimurium and produced a markedly decreased ability to produce free radicals during infection compared to wild type macrophages. Rubicondeficient cells also displayed a hyperactivation of canonical Nf-Kb signaling, demonstrating a failure to coordinate an appropriate inflammatory reaction. Rubicon-/mice demonstrate that Rubicon is essential for several aspects of pathology including replication control and immunological response.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.083
L-55
Autophagy deficient mice as a model for studying stress-induced autophagy in vivo Guillermo Mariño University of Oviedo / Principality of Asturias Sanitary Research Institute (ISPA), Oviedo, Spain
Guillermo Velasco Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain
Autophagy is the main cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles and represents the principle catabolic process regulating cellular homeostasis and organelle and protein turnover. Besides its role in cellular homeostasis, autophagy can be a form of programmed cell death or play a cytoprotective role, for example in situations of nutrient starvation. Accordingly, autophagy plays a dual role in cancer as this cellular process may help to overcome the stress evoked at the initial steps of tumorigenesis or work as a tumor suppressor mechanism. Moreover, different anticancer treatments activate autophagy in tumor cells, which either enhance cancer cell death or act as a mechanism of resistance to chemotherapy. Prior work by our group showed that Δ9-tetrahydrocannabinol (THC, the main active component of marijuana) triggers autophagy-mediated cancer cell death. In this presentation I will summarize several recent findings supporting that the modification of the sphingolipid metabolism of cancer cells by cannabinoids plays a pivotal role in the stimulation of autophagy-mediated cancer cell death.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.085