Abc Transporters in Mitochondria

Mitochondria are essential organelles of most eukaryotic cells including fungi, invertebrates, vertebrates and plants. They perform various processes such as oxidative phosphorylation, the tricarboxylic acid cycle, fatty acid oxidation, the biosynthesis of various amino acids, the generation of iron-sulfur (Fe/S) clusters and their insertion into apoproteins, as well as partial reactions of heme biosynthesis and the urea cycle. According to the endosymbiont hypothesis, virtually all of these functions have been inherited from the bacterial ancestor of the present-day mitochondrion, an -proteobacterium. Hence, both the components and mechanisms of the shared processes are highly related in mitochondria and bacteria. In contrast to the aforementioned functions, reactions including membrane transport of proteins, peptides, sugars, metabolites, vitamins and lipids into and out of the organelle differ quite significantly from those operating in bacteria. For instance, the mitochondrial protein import system involving the TOM and TIM preprotein translocases does not exist in bacteria (Neupert, 1997; Pfanner and Geissler, 2001). Likewise, only one of the bacterial protein export systems has been maintained in mitochondria, namely the Oxa1/YidC complex (Dalbey and Kuhn, 2000). Striking differences between mitochondria and bacteria also exist with respect to trafficking small molecules. To facilitate this task, mitochondria contain more than 30 so-called ‘carrier’ proteins, which transport a variety of compounds (e.g. nucleotides, diand tricarboxylates, vitamins and amino acids) across the inner membrane (reviewed by El Moualij et al., 1997; Nelson et al., 1998; Palmieri et al., 2000). No bacterial counterparts of these carrier proteins are known. Apparently, mitochondrial carrier proteins have replaced most of the versatile membrane transport functions performed by ATP-binding cassette (ABC) transporters of the bacterial ancestors of mitochondria. In presentday bacteria such as Escherichia coli, more than 50 members of this large protein family are found, and they are crucial for transport into and out of the bacterial cytosol (Linton and Higgins, 1998). In comparison, only a small number of ABC transporters exist in mitochondria. Strikingly, both structural and functional evidence suggests that these mitochondrial transporters do not closely resemble any of the bacterial counterparts, but rather represent proteins with a role specifically adapted for eukaryotic cells. Today, we can distinguish different types of mitochondrial ABC transporters. Two types belong to subclass B of the ABC transporter superfamily (MDR-like proteins) (Bauer et al., 1999; Taglicht and Michaelis, 1998) and are distinguished according to their degree of homology to the three ABC transporters present in the yeast Saccharomyces cerevisiae, namely the Atm1p-like proteins and the Mdl1p/Mdl2p-like 515