DNA AND CELL BIOLOGY Volume 34, Number 4, 2015 ª Mary Ann Liebert, Inc. P. 227 DOI: 10.1089/dna.2015.1501
EDITORIAL
Special Focus on Autophagy Sandra Morais Cardoso
A
utophagy is a homeostatic process during which cellular components are recycled through the lysosomal compartment. Although lysosomal function was disclosed in the middle of the 20th century, only in the past 15 years has substantial progress on the molecular dissection of autophagy taken place, uncovering the key components involved in different autophagic processes, their regulation, and their contribution to multiple cellular functions. This knowledge allowed scientists to study the role of autophagy in several human diseases, as it has been described that this process is induced in physiological or pathological conditions. As a catabolic process, ‘‘bulk’’ autophagy is activated upon nutrient limitations, low oxygen levels, or decreased energy supply, allowing the recycling of degradation products (e.g., amino acids) back into the cytosol to be used in crucial biosynthetic pathways. Quality control autophagy allows a precise elimination of defective organelles or protein aggregates owing to ubiquitin tags and preventing eventual deleterious effects elicited by such circumstances. Autophagy in mammalian cells can be divided into three major types: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), depending on the different pathways by which cargo is delivered to the lysosome. This special issue aims at discussing recent advances on the role of autophagy in disease, focusing on recent data from the World Health Organization, identifying chronic diseases such as heart disease, stroke, chronic respiratory diseases, and diabetes as leading causes of mortality in the world. Taken together, these under-appreciated epidemics affect high, low, and middle income countries. Additionally, age-related neurodegenerative disorders will inevitably become a significant burden to developed countries with increased life expectancy rates due to advanced health policies and valuable medical care. The issue ‘‘Autophagy in Disease’’ will focus on the role of autophagy in different physiological processes and pathologies. Inflammation is a defensive response of the organism to harmful factors triggered by infectious agents or irritants, exogenous or endogenous, but prolonged or exacerbated inflammatory responses associated with inflammasome activation are involved in many pathologies. The potential role of autophagy in inflammasome activation and disease progression/arrest will be discussed. Another chapter is focused on tuberculosis, a chronic and potentially lethal infectious disease significantly affecting countries with high rates of HIV infections. Since the tuberculosis pathogen can replicate in infected cells by arresting phagosome maturation, some innovative therapies based on autophagy manipulation aiming at bacterial elimination will be discussed. This issue will also debate the role of autophagy in cardiomyocytes—cells involved in heart function—mainly to discuss how the mechanisms and signals that regulate the autophagic process in the heart may be relevant in pathological conditions. Additionally, and because altered autophagic activity has been implicated in type 2 diabetes, hindering b cell function, this issue will present how autophagy might be targeted as a therapeutic opportunity for type 2 diabetes. Aging has been associated with a number of pathological conditions wherein cells accumulate protein aggregates and damaged organelles that need to be removed by autophagy. Post-mitotic cells such as neurons are especially vulnerable. At the cellular level Alzheimer’s disease is characterized by the accumulation of misfolded amyloid-b peptide and hyperphosphorylated tau protein, indicating that defective autophagy is a contributing factor to the pathology. Taking this into account, this issue will also debate on how autophagy can be targeted in order to efficaciously counteract AD-related symptomatic and neuropathological features. CNC–Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
227
EDITORIAL
Special Focus on Autophagy Sandra Morais Cardoso
A
utophagy is a homeostatic process during which cellular components are recycled through the lysosomal compartment. Although lysosomal function was disclosed in the middle of the 20th century, only in the past 15 years has substantial progress on the molecular dissection of autophagy taken place, uncovering the key components involved in different autophagic processes, their regulation, and their contribution to multiple cellular functions. This knowledge allowed scientists to study the role of autophagy in several human diseases, as it has been described that this process is induced in physiological or pathological conditions. As a catabolic process, ‘‘bulk’’ autophagy is activated upon nutrient limitations, low oxygen levels, or decreased energy supply, allowing the recycling of degradation products (e.g., amino acids) back into the cytosol to be used in crucial biosynthetic pathways. Quality control autophagy allows a precise elimination of defective organelles or protein aggregates owing to ubiquitin tags and preventing eventual deleterious effects elicited by such circumstances. Autophagy in mammalian cells can be divided into three major types: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), depending on the different pathways by which cargo is delivered to the lysosome. This special issue aims at discussing recent advances on the role of autophagy in disease, focusing on recent data from the World Health Organization, identifying chronic diseases such as heart disease, stroke, chronic respiratory diseases, and diabetes as leading causes of mortality in the world. Taken together, these under-appreciated epidemics affect high, low, and middle income countries. Additionally, age-related neurodegenerative disorders will inevitably become a significant burden to developed countries with increased life expectancy rates due to advanced health policies and valuable medical care. The issue ‘‘Autophagy in Disease’’ will focus on the role of autophagy in different physiological processes and pathologies. Inflammation is a defensive response of the organism to harmful factors triggered by infectious agents or irritants, exogenous or endogenous, but prolonged or exacerbated inflammatory responses associated with inflammasome activation are involved in many pathologies. The potential role of autophagy in inflammasome activation and disease progression/arrest will be discussed. Another chapter is focused on tuberculosis, a chronic and potentially lethal infectious disease significantly affecting countries with high rates of HIV infections. Since the tuberculosis pathogen can replicate in infected cells by arresting phagosome maturation, some innovative therapies based on autophagy manipulation aiming at bacterial elimination will be discussed. This issue will also debate the role of autophagy in cardiomyocytes—cells involved in heart function—mainly to discuss how the mechanisms and signals that regulate the autophagic process in the heart may be relevant in pathological conditions. Additionally, and because altered autophagic activity has been implicated in type 2 diabetes, hindering b cell function, this issue will present how autophagy might be targeted as a therapeutic opportunity for type 2 diabetes. Aging has been associated with a number of pathological conditions wherein cells accumulate protein aggregates and damaged organelles that need to be removed by autophagy. Post-mitotic cells such as neurons are especially vulnerable. At the cellular level Alzheimer’s disease is characterized by the accumulation of misfolded amyloid-b peptide and hyperphosphorylated tau protein, indicating that defective autophagy is a contributing factor to the pathology. Taking this into account, this issue will also debate on how autophagy can be targeted in order to efficaciously counteract AD-related symptomatic and neuropathological features. CNC–Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
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