17.19:
Delivery Pathways to the Lysosome
Based on the type of cargo, the cell uses four specialized delivery pathways to the lysosome— endocytosis, phagocytosis, macropinocytosis, and autophagy.
In endocytosis, receptors on the plasma membrane bind the target molecule, which can be a nutrient, a protein, or some other type of soluble substance.
A portion of the plasma membrane bends inward to surround the target finally detaching from the plasma membrane to form a transport vesicle.
Cells such as macrophages and neutrophils follow a similar pathway called phagocytosis to engulf cell debris, foreign particles, or microbes, like bacteria or protozoa. A phagocyte traps a receptor-bound particle inside a vesicle called a phagosome.
In macropinocytosis, part of the cell membrane folds inward to create tear-shaped pockets surrounding the material being taken into the cell. There are no receptors involved; therefore, the process is non-specific.
Lastly, in autophagy, the material to be digested is sequestered in a double-membrane organelle called an autophagosome.
The outer membrane of the autophagosome contains protein markers that target it for delivery to the lysosome.
In all four pathways, the vesicles ultimately fuse with the lysosome and release their contents for degradation by lysosomal enzymes.
17.19:
Delivery Pathways to the Lysosome
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated endocytosis was the first described endocytic process. The molecular machinery that generates clathrin-coated endocytic vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in specialized membrane sites, called clathrin pits, selectively recognize and bind the macromolecule to be internalized. With the cargo loaded, clathrin-coated vesicle buds off the cell membrane on the cytosolic side, carrying the macromolecule into the cell.
Christian de Duve coined "endocytosis" to mean ingestion of large particles, including bacteria, macromolecules in small vesicles, and fluid uptake. Later, these events were studied in detail and renamed phagocytosis and pinocytosis, respectively.
Phagocytosis
Phagocytosis is a type of endocytosis where cells ingest particles larger than 500 nm diameter using specialized receptors. The first studied phagocytic process was how amoeba captured their food, such as bacteria or other protozoans. Phagocytosis was also observed to play a significant role in defense against invading microorganisms and eliminating cell debris and aged or dead cells from the body in multi-cellular organisms. In mammals, macrophages, and neutrophils, two types of white blood cells, play a critical role in the body's defense system in eliminating microorganisms from infected tissue.
Pinocytosis
Pinocytosis, which means “ cell-drinking,” is more common in eukaryotic cells than phagocytosis because it is a non-specific process that usually occurs without involving receptors. This endocytic pathway is responsible for internalizing smaller particles up to 500 nm diameter and fluids. The cell membrane invaginates, capturing particles and fluids with negligible diffusion properties. The membrane encloses the isolated solutes, and fluid finally pinches off to form membrane-bound vesicles contained within the cell.
Autophagy
Autophagy or self-eating is a specialized form of endocytosis, activated in response to diverse stress and physiological conditions such as food deprivation, hyperthermia, hypoxia, and other modulators of aging. It is also involved in the cell's housekeeping by removing incorrectly obsolete or damaged organelles, folded or aggregated proteins, and invading microorganisms.
In addition to the degradation of unwanted intracellular components, autophagy enhances cell surface antigen presentation, prevents necrosis, and protects against genome instability, thus playing a pivotal role in preventing cancer, infections, neurodegenerative diseases, cardiomyopathy, diabetes, liver disease, and autoimmune diseases.
Suggested Reading
- Kaksonen, M., & Roux, A. (2018). Mechanisms of clathrin-mediated endocytosis. Nature reviews Molecular cell biology, 19(5), 313-326.
- Mizushima, N. (2007). Autophagy: process and function. Genes & development, 21(22), 2861-2873.