Lysosomes are single-membrane vesicles that present in almost all animal cells. Their diameter is about 0.5 micrometers and the quantity is around several hundred. They contain various hydrolase for breaking down proteins, nucleic acids, polysaccharides, and lipids, but these enzymes only work in an acidic environment. Therefore, proton pumps on their membrane continuously inject hydrogen ions into the interior to keep a pH of around 5. Channel protein allow certain small molecules to enter and also assist in transporting hydrolytic products into the cytoplasm. These membrane proteins are heavily coated with carbohydrates to prevent their degradation by hydrolase.
Normally, the contents would not leak out because cholesterol-rich membrane is very stable. The neutral cytosol also reduces catalysis of the leaked enzymes, even if a small amount escapes. However, it is noteworthy that even though catalysis is reduced in the cytoplasm, some acid hydrolases are still active to cause decomposition. Particularly in cases of massive leakage, the cell structure is inevitably subjected to fatal destruction. This scenario is common in physical and chemical damage, programmed cell death, and viral infections. The strong heterogeneity of lysosomes is manifested in their varying sizes, shapes, and numbers in different cells, and even at different stages within a same cell. Different hydrolases may also be synthesized to adapt to the specific metabolic pathways. In plants, their function is replaced by the large central vacuole.
Function: Lysosomes are digestive system of animal cells
Heterophagy degrades extracellular substances
Proteins and their derivatives naturally lose activity over time. This is because the fragile tertiary and quaternary structures are destroyed by intramolecular atomic vibrations, water collisions and some oxidative free radicals. If these aren’t removed promptly, they will accumulate in body to result in the degradation of biological functions. Enzymes in lysosomes are released into the extracellular matrix to dissolve collagen, elastin, and other proteins. Their fragments are eaten by surrounding cells. Vesicles envelop the engulfed materials and fuse with lysosomes where they are digested into building blocks for recycling. This explains why cosmetic procedures like Thermage have only a few months of efficacy.
Lysosomes can also digest macromolecular nutrients to nourish the organism. Some long oligopeptides enter intestinal cells via endocytosis. This is particularly true for infants who rely heavily on this mechanism to obtain proteins. However, antibodies escape degradation and are directly secreted into the bloodstream for infant passive immunity. Spherical complexes composed of lipoproteins, phospholipids, cholesterol, and fats are degraded in a similar way. For single-celled eukaryotes like amoebas, lysosomes serve as their digestive system.
Phagocytes are analogous to amoebas within animal body, and responsible for engulfing invaders. In lysosomes, hydrolytic enzymes act like gastric juices to digest bacteria and viruses. Additionally, NADPH oxidase reduces oxygen to superoxide anion to generate other reactive oxygen species (H₂O₂, HClO, ·OH) during the respiratory burst. The strongly oxidative ROS damage bacterial DNA, proteins, and lipid membranes. Apart from complete degradation, dendritic cells present antigens on their surfaces to awaken appropriate T cells they encounter. If a phagocyte consumes too much, its lysosomes may rupture to result in death. However, the sacrifice isn’t in vain; cytokines in their corpses will recruit more warriors to continue the battle. Additionally, aged cells are also engulfed by immune system. For instance, red blood cells only live for 120 days, and our immune cells need to eat all the aging red blood cells everyday.
Autophagy Digests Intracellular Substances
Another type of vesicle originates from cytoplasm. Some small denatured or misfolded proteins inside eukaryotes are recycled either in ubiquitin pathway or in microautophagy. Lysosome directly invaginates its membrane to engulf them. Some substances are too large, such as aging mitochondria or endoplasmic reticulum that needs to eliminate after detoxification. They will be marked, and then smooth ER will wrap them to form a double-membrane vesicle with a diameter of several hundred nanometers. Finally, the vesicles fuse with lysosomes. This process is called macroautophagy. Some substrates with special amino acid sequences are recognized by chaperones, and penetrate into lysosome directly via membrane proteins.
The half-life of biomacromolecules ranges from a few hours to several days. The half-life of Mitochondria takes approximately 10 days. Autophagy is in a very low level under normal conditions, but certain conditions can trigger its massive occurrence. In a state of starvation, aside from fat and glycogen for energy, the cell's organelles begin to be eaten by itself, especially aging ones. Therefore, it is believed that moderate fasting can obviously clear aging organelles and extend lifespan. The lifespan of calory-limited monkeys extends by 30-40% in experiments. In maturing red blood cells, lysosomes clear out all organelles through autophagy.
When damage is severe or during the development of multicellular organisms, hydrolases are released from lysosomes to degrade unnecessary cells and tissues. This self-destructive process is called autolysis, exemplified in the formation of fingers and toes, as well as the degeneration of a tadpole tail. If autolysis is inhibited during development, the tissue that fails to separate between fingers makes them to be partially or entirely fused.
There are numerous hydrogen bonds between elastin and collagen molecules. Some lipids aggregate to minimize surface area due to hydrophobic interactions. These difficult-to-digest substrates will be expelled from the cell via exocytosis.