Autophagy refers to the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components.
A process through which parts of the cell are degraded in the lysosome.
Autophagy is the primary intrinsic degradative system for peptides, fats, carbohydrates, and other cellular structures, and is vital for upholding the correct cellular balance.
Autophagy is the process of degradation through lysosomes which occurs when a vesicle buds off from the endoplasmic reticulum and engulfs the material, then, attaches and fuses with the lysosome to allow the material to be degraded.
Autophagy is a self-degradative mechanism that regulates energy sources during growth and reaction to dietary stress, and clears aggregated proteins, cleaning damaged structures including mitochondria and endoplasmic reticulum and eradicating intracellular infections.
Autophagy has antiviral and antibacterial roles within the cell, and it is involved at the beginning of distinctive and adaptive immune responses to viral and bacterial contamination.
Autophagy, the major degradation pathway in eukaryotic cells.
Autophagy is a process by which cells recycle and degrade their own components, including proteins, to maintain cellular homeostasis.
Autophagy is essential for the removal of damaged organelles via macroautophagy or proteins and smaller cellular debris via microautophagy from the cytoplasm.
Autophagy is a way for the cell to recycle old and damaged materials by breaking them down into their smaller components, allowing for the resynthesis of newer and healthier cellular structures.
Autophagy can thus remove protein aggregates and damaged organelles that can lead to cellular dysfunction.
Autophagy is the major intracellular degradation route in cells.
Autophagy serves to protect yourself from cytotoxicity through degradation of toxic proteins aggregates, pathogens, and damaged organelles.
Autophagy is a self-catabolic process involving sequestration of cytoplasmic contents for degradation in lysosomes.
Mutations in autophagy related genes are linked to many human diseases.
It allows the orderly degradation and recycling of cellular components.
It sustains homeostasis by recycling essential metabolites.
There is a core set of autophagy related genes (ATG) orchestrating fundamental changes of autophagy.
It involves the formation of a transient double membrane bound autophagosome that encapsulates and delivers cytoplasmic cargo to acidic sub compartments of the endolysosomal system for degradation by hydrolysis.
Autophagy helps regulate the cell’s health in times of oxidative stress.
The lysosome has a limited membrane serving as a safety mechanism, and blocks leakage of its degradative enzymes.
Autophagy involves different modes of cargo delivery to the lysosome and involves complex membrane dynamics.
Autophagy degrades damaged organelles, cell membranes and proteins
Impaired autophagy is one of the main reasons for the accumulation of damaged cells and aging.
Autophagy can be induced by ROS levels through many different pathways.
Autophagy activation in the cell in an attempt to dispose of harmful organelles and prevent damage, such as carcinogens, without inducing apoptosis.
Autophagy recycles old or damaged cell parts, which increases longevity and decreases the chances of being obese, prevents spikes of glucose concentration in the blood, leading to reduced insulin signalling.
Longevity is connected to caloric restriction and insulin sensitivity inhibiting mTOR, which in turns allows autophagy to occur more frequently.
It may be that mTOR inhibition and autophagy reduce the effects of reactive oxygen species on the body, which damage DNA and other organic material, so longevity would be increased.
mTORC1’s ability to inhibit autophagy while at the same time stimulate protein synthesis and cell growth can result in accumulations of damaged proteins and organelles, contributing to damage at the cellular level.
Because autophagy appears to decline with age, activation of autophagy may help promote longevity in humans.
Problems in proper autophagy processes have been linked to diabetes, cardiovascular disease, neurodegenerative diseases, and cancer.
There are three forms of autophagy:
macroautophagy,
microautophagy, and
chaperone-mediated autophagy (CMA).
In macroautophagy, discardable cytoplasmic constituents are targeted and isolated from the rest of the cell within a double-membraned vesicle known as an autophagosome.
The macroautophagy is the major regulated form of autophagy that response to environmental and physiological cues.
The autophagosome fuses with an available lysosome, resulting in the disposal of the contents of the vesicle.
Microautophagy involves engulfment of cytoplasmic contents by lysosomes, chaperoned-assisted translocation of substrate proteins across lysosomal membrane.
Autophagy has adaptive responses to stress, and can promote survival of the cell, but can promote cell death and morbidity.
In starvation states the breakdown of cellular components promotes cellular survival by maintaining cellular energy levels.
Lysosomes are responsible for glucagon-induced autophagy.
Macro, micro, and Chaperone mediated autophagy are mediated by autophagy-related genes and their associated enzymes.
Macroautophagy is the main pathway, to eradicate damaged cell organelles or unused proteins.
The phagophore engulfs the material that needs to be degraded, which forms a double membrane known as an autophagosome, around the organelle marked for destruction.
The autophagosome travels through the cytoplasm of the cell to a lysosome, and the two organelles fuse.
The contents of the autophagosome are degraded via acidic lysosomal hydrolase.
Microautophagy directly engulfs cytoplasmic material into the lysosome.
Macro autophagia degrades damaged mitochondria, ruptured lysosomes, and intracellular microbes.
Chaperone-mediated autophagy is a complex specific pathway, which involves the recognition by the hsc70-containing complex.
Mitophagy is the selective degradation of mitochondria by autophagy.
Mitophagy often occurs to defective mitochondria following damage, and
promotes turnover of mitochondria preventing accumulation of dysfunctional mitochondria.
The depolarization of the mitochondrial membrane is characteristic of the initiation of autophagy.
Mitochondria damage begins to release ROS, and autophagy is initiated to dispose of the damaging organelle.
Mitophagy is not limited to the damaged mitochondria but also involves undamaged ones.
Lipophagy is the degradation of lipids by autophagy.
Amino acid sensing and signals such as growth factors and reactive oxygen species regulate the activity of the protein kinases mTOR and AMPK.
These two kinases regulate autophagy through inhibitory phosphorylation.
Induction of autophagy results in the dephosphorylation and activation of the
kinases.
Cellular autophagy plays an important role in innate immunity.
Intracellular pathogens, such as Mycobacterium tuberculosis are targeted for degradation by the same cellular machinery and regulatory mechanisms that target host mitochondria for degradation.
Autophagy generally leads to the destruction of the invasive microorganism, although some bacteria can block the maturation of phagosomes .
Autophagy mediates several biologic functions in the cell, eliminates cytoplasmic material, generation of degradation products and cytoplasm-to-lysosome transport.
Autophagy’s role is adaptation to metabolic demands.
Autophagic cell death can be prompted by the over expression of autophagy where the cell digests too much of itself in an attempt to minimize the damage and can no longer survive.
Toll-like receptor activation, initiates intracellular signaling cascades leading to induction of interferon and other antiviral cytokines.
Many viruses and bacteria subvert the autophagic pathway to promote their own replication.
Galectin-8 is an intracellular receptor able to initiate autophagy against intracellular pathogens.
mTOR and AMPK inhibit and activate autophagy, respectively.
One of the mechanisms of programmed cell death is associated with the appearance of autophagosomes.
It is essential for basal homeostasis.
it is important in maintaining muscle homeostasis during physical exercise.
It is important for the ever-changing demands of their nutritional and energy needs, particularly through the metabolic pathways of protein catabolism.
Autophagy induction may contribute to the beneficial metabolic effects of exercise and that it is essential in the maintaining of muscle homeostasis during exercise.
Autophagy maintains homeostasis in collagen VI fibers.
Chaperone-assisted selective autophagy (CASA), is induced in contracting muscles and is required for maintaining the muscle sarcomere under mechanical tension.
The CASA chaperone complex recognizes damaged cytoskeleton components and through a ubiquitin-dependent autophagic sorting pathway allows lysosomes to dispose of such molecules.
CASA is necessary for maintaining muscle activity.
Autophagy decreases with age.
Autophagy is constantly activated in normal cartilage but it is compromised with age and precedes cartilage cell death and structural damage, it is involved in a normal protective process of joints.
Autophagy plays an important role in protecting against cancer as well as potentially contributing to the growth of malignancy.
Autophagy promotes survival of tumor cells that have been starved, or that degrade apoptotic mediators.
The use of inhibitors of the late stages of autophagy on cells that use autophagy to survive, increases the number of cancer cells killed by antineoplastic drugs.
Autophagy is both a tumor suppressor and a factor in tumor cell survival.
Necrosis and chronic inflammation is limited through autophagy which helps protect against the formation of tumor cells.
Autophagy, however, plays a large role in tumor cell survival, as it is used as a way to deal with stress on the cell.
Induction of autophagy is a pro-survival mechanism that improves the resistance of cancer cells to radiation.
Once these autophagy related genes were inhibited, cell death was potentiated.
Metabolic stresses including hypoxia, nutrient deprivation, and an increase in proliferation activate autophagy to recycle ATP and maintain survival of the cancerous cells.
Autophagy enables continued growth of tumor cells by maintaining cellular energy production.
Inhibiting autophagy genes in tumors cells, regression of the tumor and extended survival of the organs affected by the tumors is found.
Inhibition of autophagy has also been shown to enhance the effectiveness of anticancer therapies.
Cells undergoing extreme stress experience cell death either through apoptosis or necrosis.
With prolonged autophagy activation results in a high turnover rate of proteins and organelles.
Autophagy controls regulation of inflammation, and vice-versa.
The degradation of cellular components lysosomes during autophagy serves to recycle vital molecules and generates a building blocks to help the cell respond to a changing microenvironment.
Deregulation of the autophagy pathway and mutation of alleles regulating autophagy are believed to cause neurodegenerative diseases such as Parkinson’s disease.
With inefficient autophagy, neurons gather ubiquitinated protein aggregates and degrade.
Ubiquitinated proteins are proteins that have been tagged with ubiquitin to subsequently be degraded.
Loss of function in these genes can lead to damaged mitochondrial accumulation and protein aggregates than can lead to cellular degeneration.
Genomewide association studies have identified more than 240 risk variants that affect intracellular pathways recognizing microbial products: the autophagy pathway, which facilitates recycling of intracellular organelles and removal of intracellular microorganisms- ATG16L1, genes regulating epithelial barrier function, ECM1, and pathways regulating innate and adaptive immunity (e.g., IL23R and IL10).1,10
Parkinson’s disease is commonly caused by dysfunctional mitochondria, cellular oxidative stress, autophagic alterations and the aggregation of proteins.
Mitochondrial swelling and depolarization are seen in Parkinson”s disease.