How proteins find their organelles

A eukaryotic cell makes thousands of different proteins, and most work in just one compartment or are sent out of the cell. Even most mitochondrial and chloroplast proteins are coded by genes in the nucleus and made in the cytosol. So how does each protein get to the right place?

Proteins carry address labels

Most proteins contain a short stretch of amino acids that acts as a shipping address. These stretches are sorting signals (also called traffic signals), and specific proteins in the cell recognize each kind and deliver the protein carrying it.

Most proteins start being made the same way: a ribosome in the cytosol begins translating messenger RNA into a polypeptide. What happens next depends on the sorting signal:

Notice that peroxisomes, though part of the endomembrane system, get their proteins post-translationally. (A small number of mitochondrial and chloroplast proteins are made inside those organelles from their own genes.)

Cotranslational sorting: into the ER

A polypeptide is built starting from one end, the N-terminus (amino end). A protein bound for the ER has an ER signal sequence, a stretch of about 6–12 mostly hydrophobic (water-avoiding) amino acids, usually near the N-terminus, so it’s among the first parts to emerge from the ribosome. It’s recognized by the signal recognition particle (SRP), a complex of protein and RNA.

Each step triggers the next through a chain of protein-protein interactions, which keeps the steps in order.

Once in the ER, proteins with an ER retention signal stay put. The rest travel in vesicles to the Golgi and then on to lysosomes, vacuoles, or the plasma membrane, steered by further sorting signals.

Post-translational sorting: into a mitochondrion

Proteins for the nucleus, mitochondria, chloroplasts, and peroxisomes are finished in the cytosol first, then imported. A protein bound for the mitochondrial matrix carries a matrix-targeting sequence at its N-terminus. Import relies on chaperones, proteins that bind to other proteins and keep them from folding too early.

The protein must stay unfolded because the channels are narrow, like threading a string of beads through a straw. Without chaperones, it would start folding in the cytosol and could get stuck.

The cell as a system

Systems biology studies how new properties emerge when many parts interact, whether the system is a metabolic pathway, a cell, an organ, or a whole organism. It focuses on how the parts connect and work together rather than on each molecule alone. Viewed this way, a bacterial cell is a fairly simple system with one main compartment, while a eukaryotic cell is a system of four interacting parts:

Each part has its own structure and organization, and each also shapes how the whole cell is built and run.

Check yourselfWhat would happen to a mitochondrial matrix protein if no chaperones were available in the cytosol?

It would begin folding right after it was made. A folded protein can’t be threaded through the narrow channels in the outer and inner mitochondrial membranes, so it would likely fail to reach the matrix.