How are lysosomes and peroxisomes produced?
What are lysosomes?
Lysosomes are the cells' garbage disposal system. They degrade the products of ingestion, such as the bacterium that has been taken in by phagocytosis seen in the above cartoon. After the bacterium is enclosed in a vacuole, vesicles containing lysosomal enzymes (sometimes called primary lysosomes) fuse with it. The pH becomes more acidic and this activates the enzymes. The vacuole thus becomes a secondary lysosome and degrades the bacterium.
Lysosomes also degrade worn out organelles such as mitochondria. In this cartoon, a section of rough endoplasmic reticulum wraps itself around a mitochondrion and forms a vacuole. Then, vesicles carrying lysosomal enzymes fuse with the vesicle and the vacuole becomes an active secondary lysosome.
A third function for lysosomes is to handle the products of receptor-mediated endocytosis such as the receptor, ligand and associated membrane. In this case, the early coalescence of vesicles bringing in the receptor and ligand produces an endosome. Then, the introduction of lysosomal enzymes and the lower pH causes release, and degradation of the contents. This can be used for recycling of the receptor and other membrane components. See the Web page on Receptor mediated endocytosis for more information.
Lysosomes carry hydrolases that degade nucleotides,
proteins, lipids, phospholipids, and also remove carbohydrate, sulfate, or phosphate
groups from molecules. The hydrolases are active at an acid pH which is fortunate because
if they leak out of the lysosome, they are not likely to do damage (at pH 7.2) unless the
cell has become acidic. A Hydrogen ion ATPase is found in the membrane of lysosomes to
acidify the environment.
How and Where are lysosomal enzymes produced? Introduction to the Ribosome-Endoplasmic Reticulum Unit
Lysosomal enzymes are made with
polyribosomes and initially sequestered in the rough endoplasmic
reticulum. The left hand view of this cartoon shows the free polyribosomes connected by the mRNA. They are arranged in rosettes and these can be seen
in the cytoplasm in conventional electron micrographs. The right hand view shows the
arrangement of polyribosomes on the rough endoplasmic reticulum. Note that the
polypeptide chain (which projects down from the large subunit) is inserted through the
membrane and into the cisterna of the rough endoplasmic reticulum. It
contains an initial "signal peptide" that allows it to be recognized by the
rough endoplasmic reticulum. Signal peptide binds to a receptor and
helps anchor the polyribosomes on the surface of the rough endoplasmie
This electron micrograph shows a high magnification of a longitudinal section through the rough endoplasmic reticulum. The electron dense ribosomes are on its outside surface. Inside the sac (cisterna) is flocculent material, the newly synthesized proteins. The details of ribosomal structure cannot be appreciated in this micrograph. They look like small irregular balls on the outside of the membrane. Note that the sacs of rough endoplasmic reticulum are bridged by a junction.
How do lysosomal proteins translocate into the lumen of the rough endoplasmic reticulum?
This simplified cartoon shows that this is the first part of the protein produced. After the signal sequence is completed, protein synthesis is further inhibited. This is to allow the interaction of the signal sequence with a complex on the rough endoplasmic reticulum. In the above cartoon, note that the signal peptide is allowed to enter and essentially guide the protein into the lumen of the rough endoplasmic reticulum. Once the signal sequence is detected, protein synthesis resumes and the rest of the protein is inserted in the lumen. Note that a signal peptidase near the inner surface of the membrane works to cleave the signal sequence from the growing peptide.
The complex is actually more complicated than the above. The cartoon to the left shows a view of the signal sequence binding and interaction
Note that the signal sequence is recognized by a Recognition Particle, or SRP. This is then bound to a receptor. This complex guides the protein through a channel like region. It also consists of a docking site for the ribosome.
Once they are inside, lysosomal enzymes are processed like other proteins. Mannose and other types of sugars are attached. Mannose will serve as a basic site for the sorting signal.
How do lysosomal proteins move to the Golgi Complex?Bannykh, S and Balch WE Membrane Dynamics at the Endoplasmic Reticulum-Golgi Interface. J Cell Biol 138: 1-4 (1997)
Small vesicles bud from ER and immediately enter the tubular vesicular complex zone. This is like a train station that organizes them to enter the Golgi complex.
Area I shows budding from ER that is arranged facing a central zone at one end of the Golgi complex. These buds become vesicles and are coated with COPII protein coats.
Area II is the vesicular-tubular cluster. The vesicle then lose their COPII coat and merge with vesicles carrying all soluble and membrane proteins to the Golgi complex. This is a mixture of vesicles including secretory proteins and lysosomal enzymes.
Area III designates the entire complex which is unique in the cytoplasm. It is termed the 'export complex' and contains unique proteins that suggest it is specialized for information flow to and from ER and the Golgi complex. Again, it is like a train station, although you stay on the same train (in the same vesicle) all the way to the Golgi complex.
This drawing shows an actual interface between the ER and the Golgi complex. The "Export complex" is seen at the top of the drawing. Note that the vesicle are moving to contribute to the cis-Golgi network of vesicles and cisternae.
The movement of these special transport vesicles is an energy requiring process. If one blocks production of ATP, the transport will not happen. This drawing shows how the rough endoplasmic reticulum forms vesicles (without ribosomes attached) that carry the newly synthesized proteins to the Golgi complex.
The inside of the vesicle becomes continuous with the inside of the Golgi cisternae, so that protein groups pointing towards the inside, could eventually be directed to face the outside of the cell.
Carbohydrate groups are attached and any subunits may be joined in these cisternae. The protein is then passed to the final region of the Golgi called the "trans face". There it is placed in vacuoles that bud from this region of the Golgi complex. These may be a certain size or density, characteristic of the cell itself. The vacuoles continue to condense the proteins and the final mature secretory granule is then moved to the membrane for secretion
How does the Golgi Complex sort lysosomal enzymes?
The Golgi complex sorts the lysosomal enzyme in the Trans region. It is received from the rough endoplasmic reticulum (RER in this cartoon) in the cis region. The sorting depends on that mannose attached to the lysosomal enzymes.
It has the following steps:
To summarize: you start with a vacuole containing ingested material, or material to be destroyed. Vesicles from the Golgi complex containing lysosomal enzymes move to the vacuole and fuse with it. The hydrogen pump acidifies the interior and the enzymes are both released and activated. The material is then digested and destroyed inside the lysosome.
Lysosomes can actually be detected by
pH indicator dyes. This photograph shows dyes that indicate different pH's with different
colors. The red lysosomes (pH 5.0) are probably typical lysosomes. The blue and green
lysosomes are probably endosomes. This change can be detected if you link a ligand to
fluorescein. Fluorescein will not fluoresce at pH's lower than 6.0. Therefore, one can
follow entry of the receptor-ligand complex and then see the fluorescence disappear as the
endosome containing the complex is acidified.