Mitochondrial Protein Transport

The Transport of Proteins into Mitochondria

• Mitochondria are double membrane-enclosed organelles that specialize in ATP synthesis using energy derived from electron transport and oxidative phosphorylation.
• Although mitochondria have their own DNA, ribosomes, and other components required for protein synthesis, almost all of their proteins are encoded in the cell nucleus and imported from the cytosol.
• Each imported protein must reach the particular organelle sub-compartment in which it functions.

Mitochondrial Sub-compartments

• The inner mitochondrial membrane encloses the matrix space and forms extensive invaginations called cristae.
• The outer mitochondrial membrane is in contact with the cytosol.
• The intermembrane space is the space between the inner and outer membranes, subdivided into the crista space and intermembrane space, with protein complexes at the junctions where the cristae invaginate.
• Each sub-compartment contains a distinct set of proteins.

Protein Import into Mitochondria

• Signal sequences direct all mitochondrial precursor proteins to their appropriate mitochondrial sub-compartment.
• One or more signal sequences are necessary and sufficient for the import and correct localization of proteins.
• Protein translocators in the mitochondrial membranes recognize particular types of signals and direct ~1500 different precursor proteins from the cytosol to the appropriate sub-compartment of mitochondria.
• The TOM complex is required for the import of nearly all nucleus-encoded mitochondrial proteins.
• The TOM complex recognizes signal sequences and transports them from the cytosol into the intermembrane space.

Peroxisomes

• Peroxisomes are major sites of oxygen utilization and are found in virtually all eukaryotic cells.
• Peroxisomes contain oxidative enzymes, such as catalase and urate oxidase, at high concentrations.
• Peroxisomes use molecular oxygen and hydrogen peroxide to perform oxidation reactions.
• Peroxisomes break down fatty acid molecules through β oxidation, converting fatty acids to acetyl CoA.

Protein Import into Peroxisomes

• Integral membrane proteins of the peroxisomal membrane are first inserted into the ER and then packaged into specialized peroxisomal precursor vesicles.
• Peroxisomal proteins can be imported directly from the cytosol into preexisting peroxisomes.
• A specific sequence of three amino acids (Ser-Lys-Leu) at the C-terminus of many peroxisomal proteins functions as an import signal.
• Peroxisomal protein import is driven by ATP hydrolysis and utilizes a collection of proteins called peroxins.
• The protein translocator in the peroxisomal membrane is composed of at least six different peroxins.