Mitochondrial Protein Sorting

Mitochondria proteins are encoded by the nuclear genome and transported to the correct mitochondrial compartments by mitochondrial protein sorting.

Mitochondrial proteins are synthesized in the cytosol as unfolded or loosely folded polypeptides called precursor proteins. Each precursor protein contains a signal sequence that targets them to the mitochondria.

Cytosolic chaperones bind to the precursors to prevent their aggregation or degradation until they are transported to the mitochondria through specialized translocons.

The mitochondrial outer membrane contains a multisubunit protein complex called the translocase of the outer membrane or TOM complex. It consists of five transmembrane proteins that form a hollow, barrel-like structure with  loosely bound import receptors.

TOM import receptors recognize the signal sequences on the precursor and transfer it through the central channel.

Using energy from ATP hydrolysis, proteins targeted to the mitochondrial matrix are transferred through a second multiprotein complex called the translocase of the inner membrane or the TIM complex.

TIM23 receptor recognizes the incoming polypeptide and uses the electrochemical potential across the inner membrane to shuttle the precursor through the TIM22 channel releasing it into the mitochondrial matrix.