Ribosomes are the cell’s protein-making machines. They read the information carried by messenger RNA (mRNA) and use it to assemble amino acids into proteins. In eukaryotic cells, ribosomes can be found either free in the cytosol or attached to the surface of the rough endoplasmic reticulum (ER). These are commonly called free ribosomes and bound ribosomes.
The important point is that free and bound ribosomes are not two different kinds of ribosomes. They have essentially the same structure and can switch between the two locations. The major difference is where they are working and where the newly made protein is headed.
What are free ribosomes?
Free ribosomes are ribosomes that are not attached to a membrane. They are found in the cytosol, the fluid portion of the cell outside membrane-bound organelles.
They make proteins that will generally remain in the cytosol or be delivered to certain locations inside the cell, such as the nucleus, mitochondria, or other non-secretory destinations. A protein’s eventual destination is determined by molecular signals within the protein or its associated machinery, rather than simply by whether a ribosome happens to be free at a particular moment.
For example, many enzymes that carry out metabolic reactions in the cytosol are synthesized by free ribosomes. Proteins that function in the nucleus can also be synthesized on free ribosomes and then transported into the nucleus after or during their synthesis.
Free ribosomes may work individually, but multiple ribosomes can also translate the same mRNA at the same time. Such a group is called a polyribosome, or polysome.
What are bound ribosomes?
Bound ribosomes are ribosomes attached to the outer surface of the rough endoplasmic reticulum. The ER is a membrane network inside eukaryotic cells, and its surface appears “rough” under a microscope because of the ribosomes attached to it.
Bound ribosomes produce proteins that enter the secretory pathway. This includes many proteins that will be:
- secreted outside the cell,
- inserted into a cell membrane,
- delivered to certain membrane-bound organelles, or
- retained within the endomembrane system, such as the ER or Golgi apparatus.
As a protein is being synthesized, the growing protein chain can be directed into the ER. This allows the cell to begin processing, folding, modifying, or transporting the protein as it is made.
A protein destined to be secreted, for instance, typically begins synthesis on a ribosome in the cytosol. A signal sequence in the emerging protein directs the ribosome to the ER, where translation continues with the protein being threaded into the ER. The ribosome therefore becomes functionally associated with the ER during that process.
Free vs. bound ribosomes at a glance
| Feature | Free ribosomes | Bound ribosomes |
|---|---|---|
| Location | Cytosol | Attached to rough ER |
| Basic structure | Essentially the same | Essentially the same |
| Main role | Make proteins for the cytosol and many non-secretory destinations | Make proteins entering the secretory pathway |
| Typical products | Cytosolic proteins and many nuclear or organelle-targeted proteins | Secreted, membrane, ER, and related proteins |
| Can the ribosome change location? | Yes | Yes |
The distinction is therefore mainly about protein targeting, not about different ribosome designs.
How does a ribosome become bound to the ER?
The ribosome’s location is determined by information in the protein being synthesized.
Translation begins on a ribosome in the cytosol. If the growing protein contains an appropriate signal sequence, cellular machinery recognizes that signal and directs the ribosome toward the ER membrane. The ribosome associates with a protein-conducting channel in the ER membrane, called a translocon.
Translation then continues while the newly synthesized protein is fed through or into the ER. Depending on its molecular signals, the protein may enter the ER’s interior or become embedded in the membrane.
This process is called co-translational targeting because targeting to the ER occurs while the protein is still being synthesized.
If the newly made protein does not contain the signals that direct it to the ER, its ribosome generally remains free in the cytosol.
The same ribosome can be free or bound
One of the most important facts to understand is that a ribosome is not permanently classified as either free or bound.
A ribosome that is free in the cytosol can become associated with the ER when it begins translating an mRNA encoding a protein destined for the secretory pathway. After translation is complete, the ribosome can dissociate from the ER and return to the cytosolic pool.
This means that the terms free ribosome and bound ribosome describe a ribosome’s current association with the ER, not permanent categories of ribosomes.
The ribosomes themselves are built from ribosomal RNA and proteins and consist of two subunits. Their fundamental job—decoding mRNA and joining amino acids together—is the same in both locations.
What kinds of proteins are made on bound ribosomes?
Bound ribosomes are particularly important for proteins that must enter or interact with the secretory pathway.
Secreted proteins are a major example. Hormones and digestive enzymes that are released from cells often follow this pathway. The protein enters the ER during synthesis and can subsequently pass through the Golgi apparatus before reaching its final destination.
Membrane proteins are another major category. Proteins that become components of the plasma membrane or membranes of organelles in the endomembrane system are generally synthesized on ER-bound ribosomes. Their molecular signals determine how they become inserted into the membrane and where they are ultimately transported.
Bound ribosomes also make proteins that remain within the ER or are transported to compartments such as lysosomes.
Does “free” mean the protein stays in the cytoplasm?
Not necessarily.
This is a common oversimplification. Free ribosomes make many cytosolic proteins, but they also make proteins that will later be transported elsewhere.
For example, many nuclear proteins are synthesized on free ribosomes and then imported into the nucleus. Likewise, proteins destined for mitochondria are generally synthesized on free ribosomes in the cytosol and subsequently imported into mitochondria.
The important distinction is that these proteins do not enter the ER-based secretory pathway during their synthesis.
Mitochondria and chloroplasts also contain their own ribosomes, which are distinct from the cytosolic ribosomes discussed here. Some proteins used by these organelles are made inside the organelles themselves, while many others are made in the cytosol and imported.
Does the ER make the ribosomes different?
No. The ER does not produce a special type of ribosome that is permanently dedicated to membrane or secretory proteins.
The functional difference comes from targeting signals in the proteins being synthesized and the cellular machinery that recognizes those signals. A ribosome translating an mRNA for a cytosolic protein can remain free, while a ribosome translating an mRNA whose product is directed into the ER can become ER-bound.
This arrangement lets the cell use the same basic protein-synthesis machinery for proteins with very different destinations.
Why the distinction matters
The difference between free and bound ribosomes is ultimately a question of protein destination.
Free ribosomes primarily support protein production for the cytosol and for destinations that do not require entry into the ER during synthesis. Bound ribosomes produce proteins that enter the ER and therefore become part of the secretory or endomembrane pathway.
Rather than thinking of free and bound ribosomes as two separate machines, it is more accurate to think of them as the same ribosomal machinery operating in different cellular locations according to the destination of the protein being made.
