INTERNAL TARGETING SIGNAL OF THE BCS1 PROTEIN - A NOVEL MECHANISM OF IMPORT INTO MITOCHONDRIA

The BCS1 protein is anchored in the mitochondrial inner membrane via a single transmembrane domain and has an N-out-C-in topology. Unlike th e majority of nuclear encoded mitochondrial preproteins, the BCS1 prot ein does not contain an N-terminal targeting sequence, A positively ch arged segment of amino acids which is located immediately C-terminal t o the transmembrane domain acts as an internal targeting signal. In or der to function, we postulate that this sequence co-operates with the transmembrane domain to form a tight hairpin loop structure. This loop is translocated across the inner membrane via the MIM/mt-Hsp70 machin ery in a membrane potential-dependent manner. This novel mechanism of import and sorting of the BCS1 protein is proposed to represent a more general mechanism used by a number of inner membrane proteins.