A MORPHOLOGICAL VIEW ON MITOCHONDRIAL PROTEIN TARGETING

Mitochondrial protein targeting includes both int ramitochondrial sort ing of proteins encoded by the organellar genome and import and subseq uent sorting of nuclear encoded precursor proteins. Only a few protein s are encoded by the mitochondrial genome and synthesized in the organ ellar matrix. These include predominantly inner membrane proteins that are perhaps co-translationally inserted into this membrane. Biochemic al data suggest that insertion into the inner membrane may be confined to the inner boundary membrane. Ultrastructurally, however, a prefere ntial association of ribosomes with either inner boundary or cristae m embranes has not been established. The majority of the mitochondrial p roteins are nuclear encoded and synthesized as precursors in the cytos ol. Electron microscopic studies revealed that import of precursor pro teins is generally confined to sites where both mitochondrial envelope membranes are closely apposed. In line with these observations, bioch emical studies indicated that precursor proteins destined for the inne r membrane or matrix have to interact with the energized inner membran e to allow complete passage of the precursor through the outer membran e. As a consequence, the mitochondrial envelope membranes have to be i n close proximity at protein import sites. In isolated mitochondria di stinct sites (designated as contact sites) exist where both envelope m embranes are closely apposed and presumably stably associated. In situ , however, mitochondrial boundary membranes are in close proximity ove r large areas that cover almost the entire mitochondrial periphery. Co nsequently, the relative area of the mitochondrial surface, where both boundary membranes are in sufficient proximity for allowing protein t ranslocation, is generally larger in situ compared to that in isolated organelles. Immunocytochemical localization studies showed a rather r andom distribution of components of the mitochondrial protein transloc ation machinery over the entire mitochondrial surface and not confined to contact sites. Based on these ultrastructral data and recent bioch emical findings we propose that mitochondrial protein import sites are dynamic in nature and include relatively labile regions of close asso ciation of the boundary membranes. In vitro, however, mitochondrial pr otein import may preferentially take place at or near the presumably s table contact sites.