Finding the right organelle. Targeting signals in mitochondrial outer-membrane proteins

Abstract

The mitochondrial outer membrane contains a diverse set of proteins that includes enzymes, components of the preprotein translocation machinery, pore-forming proteins, regulators of programmed cell death, and those that control the morphology of the organelle. All these proteins, like the vast majority of mitochondrial proteins, are encoded in the nucleus, so they are synthesized in the cytosol and contain signals that are essential for their subsequent import into mitochondria. This review summarizes our current knowledge of the signals that target mitochondrial outer-membrane proteins to their correct intracellular location. In addition, the mechanisms by which these signals are decoded by the mitochondria are discussed.

Figure 1

Topologies of proteins that reside in the outer membrane of mitochondria. OM45, outer-membrane protein of 45 kDa; TMD, transmembrane domain; Tom, translocase of the outer membrane of mitochondria; VAMP1B, vesicle-associated membrane protein/synaptobrevin 1B.

Figure 2

Sequences of the transmembrane domains and their flanking regions of amino-terminally anchored outer-membrane proteins. Positively charged amino-acid residues are shown in green and negatively charged residues are shown in red. H.s., Homo sapiens; IMS, intermembrane space; OM45, outer membrane protein of 45 kDa; R.n., Rattus norvegicus; S.c., Saccharomyces cerevisiae; Tom, translocase of the outer membrane of mitochondria.

Figure 3

Sequences of tail–anchor domains of mitochondrial and endoplasmic reticulum proteins. Positively charged amino-acid residues are shown in green and negatively charged residues are shown in red. Cytb5, cytochrome b5; ER, endoplasmic reticulum; IMS, intermembrane space; mit, mitochondrial; Net+, net positive charge; OM, outer membrane; Tom, translocase of the outer membrane of mitochondria; VAMP, vesicle-associated membrane protein/synaptobrevin.