Lysosomes are tiny vesicles filled with hydrolytic enzymes (proteins which are catalyst for thousands of metabolic reactions that are required for life) which are required by cells to metabolize its nutrients and for removing dead cells from body by destroying them. They are the main site for digestion or breakdown of structures inside the cells . Proteasome on the other hand works by the process of proteolysis (chemical reaction which cleaved peptide bonds) where its main function is to destroy damaged or unwanted proteins. Enzymes involved in process of proteolysis are known as proteases. Cells require proteasomes majorly to regulate and maintain concentration of properly folded proteins and remove those that are in excess or are misfolded .
Lysosomes are membrane bound cell organelle found mostly in all animal cells except red blood cells but are rarely found in plant cells, whereas proteasomes are present in all eukaryotes (inside nucleus and in cytoplasm), archaea and in some bacteria as well [3, 4].
Comparison of Functions of lysosomes and proteasomes
When food particle is taken up or absorbed by cells, lysosomes release enzymes in order to break those molecules (sugar or protein) into usable form of energy for cells to survive. Lysosomes carry the process of digestion/breakdown of macromolecules like carbohydrates, nucleic acids, proteins and lipids as they have acidic pH , whereas proteasomes only remove misfolded/abnormal proteins formed in cells . Secondly lysosomes repair the membrane of cells, on the other hand, proteasome are responsible for differentiation of cells (work by degrading metabolic enzymes and transcription factors) and also for cell cycle regulation and cellular differentiation. Preotasomes are also helpful for cells to respond to stress, where the ubiquitin conjugated regulatory proteins are degraded. Whenever any pathogen enters human body, macrophages engulfs the pathogen and the vesicle containing pathogen is pinched off the macrophage, further this vesicle fuses with the lysosomal membrane and lysosomes respond to foreign pathogens like viruses, bacteria and some antigens which enter in cells, by digesting them using digestive/hydrolytic enzymes but proteasomes play essential role in immune system as they generate antigenic peptides which are further presented by the major histocompatibility complex I (MHC I) molecules to T cells and these T cells then clear off the pathogen and activate B cell to develop memory against those pathogens and thus the antigens are then cleared from the body [3,4].
Comparison of protein components of Lysosomes and Proteasomes
Lysosomes are made up of proteins which are basically enzymes present on the lysosomal membrane consisting of lipids. Integral membrane proteins which are specific to lysosomes are called as Lysosome Associated Membrane glycoproteins (LAMPs) for which no such clear function is found. Considering their structure, these proteins have two internal lysosome-luminal domains that are homologous and are separated by hinge region that is rich in proline content. The proteins have transmembrane region at their C-terminal extremity which is followed by a short cytoplasmic tail . As compared to lysosomes which have enzyme (protein) and an outer membrane, proteasomes subcomponents are denoted by their Svedberg sedimentation coefficient (S). In mammals, most exclusively used proteasome is 26S proteasome (~2000 kDa) which has single 20S subunit and two 19S subunits, acting as regulatory caps. The core of this proteasome is hollow which acts as an enclosed cavity where proteins are degraded. 19S subunits at each end of the core particle has many Ubiquitin binding and ATPase active sites. This portion identifies polyubiquitinylated proteins and sends them to catalytic core. An 11S particle can link with core particle in a similar way as of 19S and contribute in clearance of any foreign peptides.
Image courtesy :- McNaught, K. S. P., Olanow, C. W., Halliwell, B., Isacson, O., & Jenner, P. (2001). Failure of the ubiquitin–proteasome system in Parkinson`s disease.Nature Reviews Neuroscience, 2(8), 589-594.
In eukaryotes, 19S has 19 different proteins which are divided in two sub-assemblies, a 10-subunit lid and a 9-subunit base (of which 6 are ATPase subunits) which directly binds to 20S core particle at the α-ring. This attachment of 19S and 20S units needs binding of ATP to ATPase subunit of 19S. In order to degrade ubiquitinylated and folded proteins using assembled complex, ATP hydrolysis is required in only one step and rest steps can work by just presence of bound ATP .
Thus we can conclude by saying that lysosomes are, protein (enzyme) containing vesicles which degrade pathogens or food particle to get rid of infection or release energy respectively and proteasomes on the other hand are responsible for removing improperly folded or ubiquitinylated proteins formed in our body failing which the body’s regular functions may be altered in a negative manner.
1. Aronson, N. N., & de Duve, C. (1968). Digestive activity of lysosomes II. The digestion of macromolecular carbohydrates by extracts of rat liver lysosomes. Journal of Biological Chemistry, 243(17), 4564-4573.
2. Ding, W. X., & Yin, X. M. (2008). Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome. Autophagy, 4(2), 141-150.
4. Peters, J. M., Franke, W. W., & Kleinschmidt, J. A. (1994). Distinct 19 S and 20 S subcomplexes of the 26 S proteasome and their distribution in the nucleus and the cytoplasm. Journal of Biological Chemistry, 269(10), 7709-7718.
6. Wang, J., & Maldonado, M. A. (2006). The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. Cell Mol Immunol, 3(4), 255-261.