BIOGENESIS OF MITOCHONDRIA: IMPORT, FOLDING AND ASSEMBLY OF PROTEINS

Walter Neupert

Institut für Physiologische Chemie, Universität München, Butenandtstr.5,

81377 München

Mitochondria are made by expansion of preexisting mitochondria. New proteins are inserted into the various mitochondrial subcompartments and assemble into the numerous protein complexes active in processes such as respiration, ATP synthesis, fatty acid oxidation, amino acid metabolism, heme biosynthesis etc. All but 8-15 (depending on the species) of these proteins are encoded by nuclear genes and are synthesized on cytosolic ribosomes as preproteins. Therefore, a massive influx of proteins from the cytosol into mitochondria occurs in rapidly growing fungal cells.

Six different preprotein translocases have been identified so far in the membranes of mitochondria. The TOM complex in the outer membrane facilitates insertion of proteins into and translocation across the outer membrane. The TIM23 complex mediates translocation across the inner membrane into the matrix, and insertion of a large number of integral membrane proteins which contain matrix targeting signals into the inner membrane.

The TIM23 complex has an import motor attached at the inner face of the inner membrane which is powered by ATP hydrolysis. The TIM22 complex is specialized in the assembly of carrier proteins and some other inner membrane components lacking matrix targeting signals. A further preprotein translocase, the Oxa1p complex, facilitates the insertion of proteins into the inner membrane from the matrix side. Oxa1p does this with proteins encoded by mitochondrial DNA and translated on mitochondrial ribosomes, as well as with nuclear-encoded proteins initially imported into the matrix from the cytosol. A further translocase is the TOB complex which sits in the outer membranes and inserts b-barrel membrane proteins. These later proteins are characteristic for the outer membrane where they form pore structures. A sixth translocation device is the Mia40 – Erv1 pair that leads to import of a class of cysteine containing small proteins into the intermembrane face.

Folding of proteins in mitochondria is facilitated by several molecular chaperones. Molecular chaperones in mitochondria participate in protein translocation, de novo folding, refolding, thermotolerance, and protein degradation. Assembly of macromolecular complexes is largely a spontaneous process. In a number of cases, however, general chaperones and, in addition, more specialized chaperones assist in the ordered assembly of newly made components the into complexes such as complexes of oxidative phosphorylation.

The lecture will present some recent results on the structure and function of the TOM and TIM23 complexes and will deal with some novel findings of mitochondrial morphology and its relation to biogenetic aspects.

W. Neupert and J. Herrmann Annu. Rev. Biochem. 2007