How Does Autophagy Differ from Phagocytosis?
Autophagy Definition: Autophagy (or autophagocytosis) is the cell's normal, controlled mechanism for removing unwanted or defective components. It is derived from the Ancient Greek autóphagos, which means "self-devouring," and kytos, which means "hollow." It enables the degradation and recycling of cellular components in a controlled manner.
Autophagy Meaning: Upon being asked about autophagy meaning we can say that Autophagy (also known as autophagocytosis) is a catabolic process in which cells destroy damaged and unwanted cellular components. The action of lysosomes drives this mechanism, which aids survival during starvation by allowing the cellular energy level to be preserved.
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Since the middle of the nineteenth century, the term "autophagy" has been in use. The term autophagy was coined in 1963 by Belgian biochemist Christian de Duve, based on his discovery of the functions of the lysosome. Researchers were able to deduce the mechanisms of autophagy thanks to the discovery of autophagy-related genes in yeast in the 1990s, which contributed to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi.
Autophagy is a cytoplasmic breakdown pathway that transports cytoplasmic components to the autophagy lysosome. Despite its simplicity, recent research has shown that autophagy has a wide range of physiological and pathological functions, some of which are complex. Sequestration, transport to lysosomes, degradation, and use of degradation products are all phases of autophagy, and each one has a distinctive role.
There are Five Different Types of Autophagy:
Macroautophagy
The key mechanism is macroautophagy, which is mainly used to eliminate damaged cell organelles or unused proteins. The phagophore first engulfs the substance to be degraded, forming an autophagosome, a double membrane that surrounds the organelle to be destroyed. After that, the autophagosome passes through the cell's cytoplasm to a lysosome in mammals or vacuoles in yeast and plants, where the two organelles fuse. The contents of the autophagosome are degraded within the lysosome/vacuole by acidic lysosomal hydrolase.
Microautophagy
Microautophagy, on the other hand, includes the lysosome directly engulfing cytoplasmic material. Invagination, or the inward folding of the lysosomal membrane, or cellular protrusion, causes this.
Chaperone-Mediated Autophagy
CMA, or chaperone-mediated autophagy, is a complex and unique autophagy pathway that involves the identification of hsc70-containing complexes. This means that a protein must have the hsc70 complex's recognition site, allowing it to bind to the chaperone and form the CMA- substrate/chaperone complex. This complex then travels to a lysosomal membrane-bound protein, which recognises and binds to the CMA receptor. The substrate protein is unfolded and translocated across the lysosome membrane with the aid of the lysosomal hsc70 chaperone after it is recognised.
Mitophagy
Mitophagy is autophagy's selective destruction of mitochondria. It occurs often in defective mitochondria as a result of damage or stress. Mitophagy encourages mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria, which can lead to cell death. In yeast, it is mediated by Atg32, and in mammals, it is mediated by NIX and its regulator BNIP3. PINK1 and parkin proteins control mitophagy. Mitophagy does not only affect weakened mitochondria; it also affects healthy mitochondria.
Lipophagy
Lipophagy is the autophagic degradation of lipids, a feature that has been demonstrated in both animal and fungal cells. Lipophagy's role in plant cells, on the other hand, is unknown. Lipid droplets (LDs), spheric "organelles" with a centre of mostly triacylglycerols (TAGs) and a unilayer of phospholipids and membrane proteins, are the object of lipophagy. The major lipophagic process in animal cells is macroautophagy, which involves the phagophore engulfing LDs. Microplipophagy, on the other hand, is the key mechanism in fungal cells and is particularly well studied in the budding yeast Saccharomyces cerevisiae. Lipophagy was first observed in mice and became widely known after that.
Autophagy Functions
Nutrient Starvation - Autophagy is involved in a number of biological activities. One example is in yeasts, where food deprivation causes a high amount of autophagy. This enables the degradation of unnecessary proteins and the recycling of amino acids for the synthesis of proteins that are required for survival. Autophagy is initiated in higher eukaryotes in reaction to nutrition depletion, which occurs in newborn animals after cutting off the trans-placental food supply, as well as in nutrient-starved cultured cells and tissues.
Xenophagy - Xenophagy is the autophagic destruction of pathogenic particles in microbiology. Innate immunity relies heavily on the cellular autophagic machinery. Intracellular pathogens, such as Mycobacterium TB (the tuberculosis-causing bacteria), are degraded by the same cellular machinery and regulatory systems that degrade host mitochondria. This provides, incidentally, more support for the endosymbiotic hypothesis. Although some bacteria can prevent phagosomes from maturing into degradative organelles called phagolysosomes, this process usually results in the demise of the invasive pathogen.
Infection - The autophagosome is thought to extract vesicular stomatitis virus from the cytosol and translocate it to the endosomes, where it is detected by a pattern recognition receptor called toll-like receptor 7, which detects single-stranded RNA. Intracellular signalling cascades are activated once the toll-like receptor is activated, leading to the generation of interferon and other antiviral cytokines. To boost their own replication, certain viruses and bacteria sabotage the autophagic pathway.
Repair Mechanism -Autophagy is regarded to be one of the key reasons for the accumulation of damaged cells and ageing since it degrades damaged organelles, cell membranes, and proteins. Autophagy and autophagy regulators are involved in the response to lysosomal injury and are generally guided by galectins like galectin-3 and galectin-8, which recruit receptors like TRIM16 and NDP52, as well as directly affect mTOR and AMPK activity, whereas mTOR and AMPK inhibit and stimulate autophagy, respectively.
Programmed Cell Death - One of the methods of programmed cell death (PCD) is autophagosome formation, which is dependent on autophagy proteins. This type of cell death is most likely related to a morphologically defined process known as autophagic PCD.
Difference between Autophagy and Phagocytosis
FAQs on Autophagy Explained: Types, Functions & Importance
1. What is autophagy and what are its main steps?
Autophagy, which literally means 'self-eating', is a fundamental catabolic process in biology where a cell breaks down and recycles its own damaged or unnecessary components. It is a crucial mechanism for maintaining cellular homeostasis. The process involves several key steps:
Initiation and Nucleation: The process begins with the formation of a double-membraned vesicle known as a phagophore or isolation membrane.
Elongation and Sequestration: The phagophore expands and engulfs cellular components targeted for degradation, such as old organelles, misfolded proteins, or pathogens. This fully enclosed vesicle is now called an autophagosome.
Fusion: The autophagosome then moves through the cytoplasm and fuses with a lysosome, an organelle filled with digestive enzymes.
Degradation and Recycling: The enzymes within the newly formed autolysosome break down the engulfed material into basic building blocks like amino acids and fatty acids, which are then released back into the cytoplasm for the cell to reuse.
2. What is the primary role of autophagy in maintaining cellular health?
The primary role of autophagy is to act as a cellular quality control system, essential for survival, differentiation, and development. It maintains cellular health by:
Removing Damaged Components: It clears out old, dysfunctional, or damaged organelles (like mitochondria) and toxic, misfolded protein aggregates, preventing their harmful accumulation.
Providing Energy: During periods of nutrient starvation, autophagy breaks down non-essential components to provide energy and molecular building blocks for essential cellular functions.
Defence Against Pathogens: It can capture and eliminate invading intracellular pathogens like bacteria and viruses, a process known as xenophagy.
By performing these functions, autophagy helps prevent conditions such as neurodegeneration, cancer, and infections.
3. How does autophagy differ from apoptosis and phagocytosis?
While all three are cellular processes involving degradation, they have distinct functions:
Autophagy: This is a cell survival mechanism. It involves the degradation of a cell's internal components within lysosomes to recycle materials and maintain homeostasis.
Apoptosis: This is programmed cell death or 'cell suicide'. It is a process where the entire cell is systematically dismantled and removed when it is old, damaged, or no longer needed. It is a mechanism of cell removal, not recycling for survival.
Phagocytosis: This is a process where a cell engulfs large external particles, such as bacteria, foreign debris, or other dead cells. It is primarily performed by specialised immune cells and is a key part of the immune response.
4. What triggers autophagy in the body?
Autophagy is primarily triggered by cellular stress. The most potent and well-studied trigger is nutrient deprivation, such as a lack of amino acids or glucose. When the cell senses low energy levels, it activates autophagy to recycle internal components and generate fuel. Other stressors that can induce autophagy include oxidative stress, hypoxia (low oxygen), DNA damage, and infection by pathogens.
5. Why is the discovery of autophagy considered a Nobel Prize-winning achievement?
The discovery of the mechanisms of autophagy earned Yoshinori Ohsumi the 2016 Nobel Prize in Physiology or Medicine because it revealed a fundamental paradigm in cell biology. His work identified the key genes and pathways controlling this process, transforming it from a mere observation to a major field of study. This understanding is critical because disruptions in the autophagy process are linked to numerous human diseases, including Parkinson's disease, type 2 diabetes, and various cancers. The discovery opened up new avenues for developing therapies that target autophagy to treat these conditions.
6. Can autophagy have any negative effects on the body?
Yes, while autophagy is generally a protective and beneficial process, it can have negative effects under certain conditions. It is a double-edged sword. For instance, in the context of cancer, while autophagy can suppress tumour initiation by removing damaged components, established tumours can hijack the process. Cancer cells in a tumour's core, which are often starved of nutrients and oxygen, can use autophagy to survive and resist treatments like chemotherapy. Therefore, in some advanced cancers, inhibiting autophagy is being explored as a therapeutic strategy.
