The preprotein translocase of the mitochondrial inner membrane: Function and evolution

Growing mitochondria acquire most of their proteins by the uptake of mitoch ondrial preproteins from the cytosol. To mediate this protein import, both mitochondrial membranes contain independent protein transport systems: the Tom machinery in the outer membrane and the Tim machinery in the inner memb rane. Transport of proteins across the inner membrane and sorting to the di fferent inner mitochondrial compartments is mediated by several protein com plexes which have been identified in the past years. A complex containing t he integral membrane proteins Tim17 and Tim23 constitutes the import channe l for preproteins containing amino-terminal hydrophilic presequences. This complex is associated with Tim44-which serves as an adaptor protein for the binding of mtHsp70 to the membrane. mtHsp70, a 70 kDa heat shock protein o f the mitochondrial matrix, drives the ATP-dependent import reaction of the processed preprotein after cleavage of the presequence. Preproteins contai ning internal targeting information are imported by a separate import machi nery, which consists of the intermembrane-space proteins Tim9, Tim10, and T im12, and the inner membrane proteins Tim22 and Tim54. The proteins Tim17, Tim22, and Tim23 have in common a similar topology in the membrane and a ho mologous amino acid sequence. Moreover, they show a sequence similarity to OEP16, a channel-forming amino acid transporter in the outer envelope of ch loroplasts, and to LivH, a component of a prokaryotic amino acid permease, defining a new PRAT-family of preprotein and amino acid transporters. (C) 1 999 Academic Press.