-
Oxidative Medicine and Cellular... 2019Macroautophagy is an evolutionarily conserved process of the lysosome-dependent degradation of damaged proteins and organelles and plays an important role in cellular... (Review)
Review
Macroautophagy is an evolutionarily conserved process of the lysosome-dependent degradation of damaged proteins and organelles and plays an important role in cellular homeostasis. Macroautophagy is upregulated after myocardial infarction (MI) and seems to be detrimental during reperfusion and protective during left ventricle remodeling. Identifying new regulators of cardiac autophagy may help to maintain the activity of this process and protect the heart from MI effects. Recently, it was shown that noncoding RNAs (microRNAs and long noncoding RNAs) are involved in autophagy regulation in different cell types including cardiac cells. In this review, we summarized the role of macroautophagy in the heart following MI and we focused on the noncoding RNAs and their targeted genes reported to regulate autophagy in the heart under these pathological conditions.
Topics: Autophagy; Humans; Myocardial Infarction; RNA, Untranslated
PubMed: 31341537
DOI: 10.1155/2019/8438650 -
Journal of Molecular Medicine (Berlin,... Nov 2016Autophagy is a major degradation pathway that engulfs, removes, and recycles unwanted cytoplasmic material including damaged organelles and toxic protein aggregates. One... (Review)
Review
Autophagy is a major degradation pathway that engulfs, removes, and recycles unwanted cytoplasmic material including damaged organelles and toxic protein aggregates. One type of autophagy, macroautophagy, is a tightly regulated process facilitated by autophagy-related (Atg) proteins that must communicate effectively and act in concert to enable the de novo formation of the phagophore, its maturation into an autophagosome, and its subsequent targeting and fusion with the lysosome or the vacuole. Autophagy plays a significant role in physiology, and its dysregulation has been linked to several diseases, which include certain cancers, cardiomyopathies, and neurodegenerative diseases. Here, we summarize the key processes and the proteins that make up the macroautophagy machinery. We also briefly highlight recently uncovered molecular mechanisms specific to neurons allowing them to uniquely regulate this catabolic process to accommodate their complicated architecture and non-dividing state. Overall, these distinct mechanisms establish a conceptual framework addressing how macroautophagic dysfunction could result in maladies of the nervous system, providing possible therapeutic avenues to explore with a goal of preventing or curing such diseases.
Topics: Animals; Autophagosomes; Autophagy; Humans; Membrane Fusion; Models, Biological; Neurons
PubMed: 27544281
DOI: 10.1007/s00109-016-1461-9 -
Autophagy Nov 2020Macroautophagy/autophagy is an intracellular degradative pathway that is often induced as a pro-survival process for cells under stress. A few recent reports establish... (Review)
Review
Macroautophagy/autophagy is an intracellular degradative pathway that is often induced as a pro-survival process for cells under stress. A few recent reports establish the role of the glycogen metabolic pathway in neuronal cell survival in conditions such as oxidative stress and hypoxia, and the possible link between glycogen synthesis and autophagy induction. This commentary highlights the emerging role of GYS (glycogen synthase) in neuronal autophagy and stress response.
Topics: Animals; Autophagy; Cell Survival; Glycogen; Humans; Macroautophagy; Neurons; Oxidative Stress
PubMed: 32718210
DOI: 10.1080/15548627.2020.1802090 -
EMBO Reports Sep 2023Lysosomal membrane damage represents a threat to cell viability. As such, cells have evolved sophisticated mechanisms to maintain lysosomal integrity. Small membrane...
Lysosomal membrane damage represents a threat to cell viability. As such, cells have evolved sophisticated mechanisms to maintain lysosomal integrity. Small membrane lesions are detected and repaired by the endosomal sorting complex required for transport (ESCRT) machinery while more extensively damaged lysosomes are cleared by a galectin-dependent selective macroautophagic pathway (lysophagy). In this study, we identify a novel role for the autophagosome-lysosome tethering factor, TECPR1, in lysosomal membrane repair. Lysosomal damage promotes TECPR1 recruitment to damaged membranes via its N-terminal dysferlin domain. This recruitment occurs upstream of galectin and precedes the induction of lysophagy. At the damaged membrane, TECPR1 forms an alternative E3-like conjugation complex with the ATG12-ATG5 conjugate to regulate ATG16L1-independent unconventional LC3 lipidation. Abolishment of LC3 lipidation via ATG16L1/TECPR1 double knockout impairs lysosomal recovery following damage.
Topics: Microtubule-Associated Proteins; Autophagy; Macroautophagy; Galectins; Lysosomes; Autophagy-Related Proteins
PubMed: 37381828
DOI: 10.15252/embr.202356841 -
Autophagy Nov 2023SQSTM1/p62: Sequestosome-1; HSP27: Heat shock protein 27; LLPS: liquid-liquid phase separation; iPSC: induced pluripotent stem cell; PB1: Phox and Bem1p; FRAP:...
SQSTM1/p62: Sequestosome-1; HSP27: Heat shock protein 27; LLPS: liquid-liquid phase separation; iPSC: induced pluripotent stem cell; PB1: Phox and Bem1p; FRAP: fluorescence recovery after photo-bleaching; ATG: autophagy-related; ALS: amyotrophic lateral sclerosis.
Topics: Humans; Sequestosome-1 Protein; HSP27 Heat-Shock Proteins; Macroautophagy; Autophagy; Amyotrophic Lateral Sclerosis
PubMed: 37194327
DOI: 10.1080/15548627.2023.2210943 -
Current Biology : CB Jan 2013Macroautophagy is an essential cellular pathway mediating the lysosomal degradation of defective organelles, long-lived proteins and a variety of protein aggregates.... (Review)
Review
Macroautophagy is an essential cellular pathway mediating the lysosomal degradation of defective organelles, long-lived proteins and a variety of protein aggregates. Similar to other intracellular trafficking pathways, macroautophagy involves a complex sequence of membrane remodeling and trafficking events. These include the biogenesis of autophagosomes, which engulf portions of cytoplasm at specific subcellular locations, and their subsequent maturation into autophagolysosomes through fusion with the endo-lysosomal compartment. Although the formation and maturation of autophagosomes are controlled by molecular reactions occurring at the membrane-cytosol interface, little is known about the role of lipids and their metabolizing enzymes in this process. Historically dominated by studies on class III phosphatidylinositol 3-kinase (also known as Vps34) and its product phosphatidylinositol-3-phosphate, as well as on the lipidation of Atg8/LC3-like proteins, this area of research has recently expanded, implicating a variety of other lipids, such as phosphatidic acid and diacylglycerol, and their metabolizing enzymes in macroautophagy. This review summarizes this progress and highlights the role of specific lipids in the various steps of macroautophagy, including the signaling processes underlying macroautophagy initiation, autophagosome biogenesis and maturation.
Topics: Animals; Autophagy; Lipids; Lysosomes; Models, Biological; Organelles; Phosphatidylinositols; Signal Transduction; Sphingolipids
PubMed: 23305670
DOI: 10.1016/j.cub.2012.10.041 -
The FEBS Journal Jan 2022Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional... (Review)
Review
Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional organelles, foreign pathogens and other cellular components. Hence, autophagy can be nonselective, where bulky portions of the cytoplasm are degraded upon stress, or a highly selective process, where preselected cellular components are degraded. To distinguish between different cellular components, autophagy employs selective autophagy receptors, which will link the cargo to the autophagy machinery, thereby sequestering it in the autophagosome for its subsequent degradation in the lysosome. Autophagy receptors undergo post-translational and structural modifications to fulfil their role in autophagy, or upon executing their role, for their own degradation. We highlight the four most prominent protein modifications - phosphorylation, ubiquitination, acetylation and oligomerisation - that are essential for autophagy receptor recruitment, function and turnover. Understanding the regulation of selective autophagy receptors will provide deeper insights into the pathway and open up potential therapeutic avenues.
Topics: Acetylation; Autophagosomes; Autophagy; Homeostasis; Humans; Lysosomes; Macroautophagy; Phosphorylation; Protein Processing, Post-Translational; Proteomics; Ubiquitination
PubMed: 33730405
DOI: 10.1111/febs.15824 -
Autophagy Jun 2020Macroautophagy/autophagy is implicated in the maintenance of normal neuronal activity through the regulation of synaptic function and plasticity. However, differences in...
UNLABELLED
Macroautophagy/autophagy is implicated in the maintenance of normal neuronal activity through the regulation of synaptic function and plasticity. However, differences in autophagic degradation within different classes of neurons have not been examined. We have recently demonstrated that autophagy plays very different roles in the two closely related principal neurons of the striatum - the spiny projection neurons of the direct (dSPN) and indirect (iSPN) pathways. Behavioral and electrophysiological experiments revealed that the absence of autophagy in either of these SPN pathways produces unique effects on motor learning, dendritic length, and intrinsic excitability. Specifically, autophagy is required for the normal development of synaptic inputs onto dSPNs, while being required for intrinsic excitability in iSPNs. In iSPNs, this occurs through the regulation of the activity of the KCNJ/Kir2 ion channel, and provides a first demonstration of autophagic control of neuronal intrinsic excitability.
ABBREVIATIONS
ASD: autism spectrum disorders; dSPNs: direct pathway spiny projection neurons; iSPNs: indirect pathway spiny projection neurons; Kir2: inwardly rectifying potassium channel 2.
Topics: Autophagy; Corpus Striatum; Macroautophagy; Neostriatum; Neurons
PubMed: 32174203
DOI: 10.1080/15548627.2020.1743070 -
The International Journal of... 2019Autophagy is subdivided into chaperone-mediated autophagy, microautophagy and macroautophagy and is a highly conserved intracellular degradative pathway. It is crucial... (Review)
Review
Autophagy is subdivided into chaperone-mediated autophagy, microautophagy and macroautophagy and is a highly conserved intracellular degradative pathway. It is crucial for cellular homeostasis and also serves as a response to different stresses. Here we focus on macroautophagy, which targets damaged organelles and large protein assemblies, as well as pathogenic intracellular microbes for destruction. During this process, cytosolic material becomes enclosed in newly generated double-membrane vesicles, the so-called autophagosomes. Upon maturation, the autophagosome fuses with the lysosome for degradation of the cargo. The basic molecular machinery that controls macroautophagy works in a sequential order and consists of the ATG1 complex, the PtdIns3K complex, the membrane delivery system, two ubiquitin-like conjugation systems, and autophagy adaptors and receptors. Since the different stages of macroautophagy from initiation to final degradation of cargo are tightly regulated and highly conserved across eukaryotes, simple model organisms in combination with a wide range of techniques contributed significantly to advance our understanding of this complex dynamic process. Here, we present the social amoeba Dictyostelium discoideum as an advantageous and relevant experimental model system for the analysis of macroautophagy.
Topics: Animals; Autophagosomes; Autophagy; Caenorhabditis elegans; Class II Phosphatidylinositol 3-Kinases; Cytosol; Dictyostelium; Drosophila melanogaster; Homeostasis; Lysosomes; Phagocytosis; Saccharomyces cerevisiae; Ubiquitin
PubMed: 31840786
DOI: 10.1387/ijdb.190186LE -
The Journal of Biological Chemistry Jul 2022Autophagy is an essential cellular process involving degradation of superfluous or defective macromolecules and organelles as a form of homeostatic recycling. Initially... (Review)
Review
Autophagy is an essential cellular process involving degradation of superfluous or defective macromolecules and organelles as a form of homeostatic recycling. Initially proposed to be a "bulk" degradation pathway, a more nuanced appreciation of selective autophagy pathways has developed in the literature in recent years. As a glycogen-selective autophagy process, "glycophagy" is emerging as a key metabolic route of transport and delivery of glycolytic fuel substrate. Study of glycophagy is at an early stage. Enhanced understanding of this major noncanonical pathway of glycogen flux will provide important opportunities for new insights into cellular energy metabolism. In addition, glycogen metabolic mishandling is centrally involved in the pathophysiology of several metabolic diseases in a wide range of tissues, including the liver, skeletal muscle, cardiac muscle, and brain. Thus, advances in this exciting new field are of broad multidisciplinary interest relevant to many cell types and metabolic states. Here, we review the current evidence of glycophagy involvement in homeostatic cellular metabolic processes and of molecular mediators participating in glycophagy flux. We integrate information from a variety of settings including cell lines, primary cell culture systems, ex vivo tissue preparations, genetic disease models, and clinical glycogen disease states.
Topics: Autophagy; Glycogen; Glycogenolysis; Macroautophagy
PubMed: 35654138
DOI: 10.1016/j.jbc.2022.102093