IMPORTANCE OF MITOCHONDRIAL TRANSMEMBRANE PROCESSES IN HUMAN MITOCHONDRIOPATHIES

In a substantial group of subjects suspected to have a mitochondriopat hy no defect in the mitochondrial energy metabolism (pyruvate dehydrog enase complex or respiratory chain complexes) can be demonstrated. At least in some of these subjects it seems justified to consider a defec t in one of the proteins which mediate the transport of several ions a nd substrates across the mitochondrial membranes. Of particular intere st are proteins which are directly involved in the process of oxidativ e phosphorylation, such as the adenine nucleotide translocator (ANT) a nd the phosphate carrier (PiC). However, defects in transmembrane ion transporters also may induce impaired energy metabolism probably as a result of osmotic disturbances within the mitochondrial matrix. In thi s respect, the voltage-dependent anion channel (VDAC) and other ion ch annels have to be taken into consideration. Here we review the still i ncomplete knowledge of the occurrence of ANT, PiC, VDAC, cation channe ls, and a few substrate carriers in human tissues, as well as their po ssible role in pathology.