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In biology, a phagolysosome, or endolysosome, is a body formed by the fusion of a phagosome with a lysosome in a process that occurs during phagocytosis. Formation of phagolysosomes is essential for the intracellular destruction of and . It takes place when the phagosome's and lysosome's membranes 'collide', at which point the lysosomal contents—including hydrolytic enzymes—are discharged into the phagosome in an explosive manner and digest the particles that the phagosome had ingested. Some products of the digestion are useful materials and are moved into the cytoplasm; others are exported by exocytosis. [[File:Phagocytosis.svg|thumb|500x500px|The process of phagocytosis showing phagolysosome formation. Lysosome(shown in green) fuses with phagosome to form a phagolysosome. ]] Membrane fusion of the phagosome and lysosome is regulated by the Rab5 protein, a G protein that allows the exchange of material between these two but prevents complete fusion of their membranes.
When the phagosome and lysosome interact with one another, they form a fully developed phagolysosome. A fully developed phagolysosome consists of digestive and aseptic properties. The purpose of phagolysosomes is to act as a protective barrier. It is a defense line that kills pathogenic bacteria that may have slipped through detection of the other immune system cells. The extracellular space that surrounds the lysosome is very acidic which is important for degradation because most cells cannot handle an acidic environment and will die, with an exception of a few.
Microbes are destroyed within phagolysosomes by a combination of oxidation and non-oxidative processes. The oxidative process, also known as respiratory burst includes the "non-mitochondrion" production of reactive oxygen species.
By lowering pH and concentrations of sources of carbon and nitrogen, phagolysomes inhibit growth of fungi. An example is the inhibition of in Candida albicans.
In human , the phagolysosomes destroy pathogens also by producing hypochlorous acid.
Interestingly, some Protein are involved in multiple stages of this process, indicating mechanistic overlap between these seemingly discrete steps. The entire process is regulated by conserved proteins involved in recognizing, engulfing, and processing extracellular debris.
Research using model organisms, particularly Caenorhabditis elegans, has been instrumental in identifying the molecular players involved in these stages and ordering them into distinct pathways. C. elegans offers several advantages for studying phagocytosis, including the ability to observe the process in live animals with endogenous cargos in situ. The predictable timing of cell deaths and engulfment in C. elegans allows for time-lapse imaging of each step at the single-cell level.
Process of Resolution [[File:Amino_Acid_Transport_&_Phagolysosome_Resolution.jpg|thumb|261x261px|Amino acid transport and phagolysosome resolution in three stages: (A) Inside the phagolysosome, hydrolases break down proteins into amino acids, represented by pink and blue dots. Amino acid transporters, such as LAAT-1 (shown in pink) and SLC-36.1 (shown in blue), export these different amino acids from the phagolysosome lumen into the cytosol.
(B) The exported amino acids activate mTOR (depicted in green). This activation leads to ARL-8-mediated tubulation. ARL-8 (shown in red) likely interacts with motor proteins and microtubules (represented in orange) to facilitate this process.(C) The tubulation process results in the formation of phagolysosomal vesicles. This cycle repeats until the phagolysosome is fully resolved.]] After phagosome-lysosome fusion, the process of resolution can occur. Degradation begins with the breakdown of the cargo membrane to expose the cargo contents to lysosomal Hydrolase. Lysosomal lipase are thought to target the cargo membrane while leaving the phagolysosomal membrane intact, possibly due to protection by glycosylated lysosomal membrane proteins. However, the exact mechanism by which lipases distinguish between these membranes remains unclear.
Once the cargo membrane is compromised, lysosomal Protease and Nuclease, such as the cathepsin protease CPL-1 and the DNase II homolog NUC-1, degrade the phagolysosomal cargo proteins and nucleic acids. The resulting breakdown products, including Amino acid, are then transported out of the phagolysosome by various transporters, including members of the solute carrier family like SLC-36.1 and the SLC66A1 ortholog LAAT-1.
The transport of breakdown products out of the phagolysosome serves multiple cellular functions. In immune cells, this process is crucial for antigen presentation, enabling the cell to communicate information about the degraded material to other components of the immune system. Additionally, the breakdown of phagolysosomal contents may contribute to cellular metabolism. The resulting molecules can serve as raw materials and energy sources for various cellular processes, potentially including the facilitation of subsequent rounds of phagocytosis. This efficient recycling of engulfed material highlights the phagolysosome's role not only in cellular defense but also in nutrient acquisition and energy management.
Membrane Dynamics
Recent time-lapse studies have revealed dynamic changes in phagolysosomal membranes during resolution. Within an hour of cargo membrane breakdown, the phagolysosome begins to tubulate and release vesicles. This process depends on the small GTPase ARL-8, which is associated with kinesin microtubule Motor protein. The released phagolysosomal vesicles play dual roles: they promote further degradation of cargo molecules and contribute to the reformation of lysosomes by retrieving lysosomal hydrolases and membrane proteins.
Signaling and Regulation
The export of degraded phagolysosomal contents, particularly Amino acid, plays a crucial role in regulating phagolysosome resolution. Amino acid transport by proteins such as SLC-36.1 and subsequent amino acid sensing lead to mTOR signaling, which is necessary for phagolysosome tubulation and vesicle release. However, the exact mechanism linking mTOR signaling to ARL-8-mediated tubulation is not yet fully understood.
Importance for Cell Function
Phagolysosome resolution serves several important cellular functions:
Despite recent advances, many aspects of phagolysosome resolution remain to be elucidated, including the specificity of lipases in membrane breakdown, potential Cytosol repair mechanisms for the phagolysosomal membrane, and the precise regulation of ARL-8 in promoting tubulation versus whole organelle movement.
Similarly, when in its amastigote stage, Leishmania obtains all its purine sources, various vitamins, and a number of its essential amino acids from the phagolysosome of its host. Leishmania also obtain heme from the proteolysis of proteins in the host phagolysosome.
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