Principles of control over formation of structures responsible for respiratory functions of mitochondria.

Topogenesis of mitochondrial proteins includes their synthesis in cytosol and mitochondria, their translocation across the outer and inner membranes, sorting to various mitochondrial compartments, and assembly of different protein complexes. These complexes are involved in transport functions, electron transfer through the respiratory chain, generation of transmembrane electrochemical potential, oxidative phosphorylation of ADP into ATP, etc. To perform these functions, a special stringent control is required over formation of submitochondrial structures and the mitochondrion as a whole. Such control is expected to rigorously eliminate not only misfolded proteins but also incorrectly incorporated subunits and is realized in mitochondria by means of numerous proteases with different functions and localizations. In the case of more complicated protein formations, e.g. supercomplexes, the protein quality is assessed by their ability to realize the integral function of the respiratory chain and, thus, ensure the stability of the whole system. Considering supercomplexes of the mitochondrial respiratory chain, the present review clearly demonstrates that this control is realized by means of various (mainly vacuolar) proteases with different functions and localizations. The contemporary experimental data also confirm the author's original idea that the general mechanism of assembly of subcellular structures is based on the "selection by performance criterion" and "stabilization by functioning".