Today in class, a student asked whether the positive charge of the presequence of proteins being imported into the mitochondria was inhibitory for entry into the intermembrane space because of the positive charge present in this compartment of the mitochondria. How do proteins get past this? Wouldn't the net positive charge be inhibitory to import through the TOM complex?

Mitochondrial proteins enter the organelle through channels formed by membrane proteins present in its inner and outer membranes.

Explanation:

All the biological membranes have lipid bilayer with the non-polar core that does not allow entry of charged and large substances. Mitochondrial proteins are synthesized in the cytosol and the unfolded proteins bind to the chaperons that deliver them to the receptors present in the outer mitochondrial membrane.

The receptor moves the protein to the membrane channels formed by integral membrane proteins of inner and outer mitochondrial membranes. The proteins enter the intermembrane space and are targeted to the inner membrane through channels while chaperons are left outside only.