Protein Transport into and Across the Mitochondrial Outer Membrane: Recognition, Insertion and Translocation of Preproteins

Abstract

The compartmentation of cells requires the accurate subcellular sorting of proteins after their synthesis on cytoplasmic ribosomes. Any cellular membrane possesses a distinct transport machinery which specifically recognizes, inserts and translocates precursor proteins destined for this particular membrane or organelle (for reviews see articles in Neupert and Lill, 1992). For instance, preproteins are inserted into the membrane of the endoplasmic reticulum and become translocated into the lumen by the action of the Sec61 and Sec63 complexes (see Rapoport et al. , this issue). For mitochondria, the transport process is particularly complex, since these organelles are bounded by two membranes, the outer and inner membrane which enclose the intermembrane space and the matrix, and separate the mitochondrion from the cytoplasm. The sub-compartmentation requires distinct sub-organellar sorting pathways which ensure the accurate distribution of the proteins. Despite the complexity of the sorting process, our knowledge about the mechanisms and the machinery of mitochondrial protein translocation has well advanced during the last decade (for recent reviews see Pfanner and Neupert, 1990; Glick and Schatz, 1991; Segui-Real et al. , 1993b; Schwarz and Neupert, 1994). In this contribution, we will focus mainly on our investigations on mechanistic aspects underlying protein transport across the mitochondrial outer membrane. The identification and properties of the components of the receptor complex have been reviewed in depth elsewhere (Kiebler et al. , 1993a; Lill et al. , 1994). For a detailed description of the events occurring at the mitochondrial inner membrane, the reader is referred to another article in this issue (Schneider et al. ).