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2.A.54 The Mitochondrial Tricarboxylate Carrier (MTC) Family

The MTC family consists of a limited number of homologues, all from eukaryotes. A single member of the family has been functionally characterized and sequenced. This is the tricarboxylate carrier from rat liver mitochondria. It is 357 amino acyl residues in length with 5 or 6 putative transmembrane α-helical spanners (TMSs). It does not exhibit internal repeats or show homology to proteins of the mitochondrial carrier family (TC #2.A.29). Homologues are found in Caenorhabditis elegans, Saccharomyces cerevisiae and Leishmania major. They are of 285-293 amino acyl residues with one exception, and are reported to possess 3-6 putative TMSs.

The rat liver mitochondrial tricarboxylate carrier has been reported to transport citrate, cis-aconitate, threo-D-isocitrate, D- and L-tartrate, malate, succinate and phosphoenolpyruvate. Trans-aconitate, α-ketoglutarate and malonate are not substrates. It presumably functions by a proton symport mechanism for the uptake of the variety of anionic substrates listed above.

The generalized transport reaction catalyzed by the MTC protein of rat liver mitochondria is therefore probably:

anionic substrate (out) + nH+ (out)  anionic substrate (in) + nH+ (in)

References associated with 2.A.54 family:

Azzi, A., M. Glerum, R. Koller, W. Mertens and S. Spycher (1993). The mitochondrial tricarboxylate carrier. J. Bioenerg. Biomembr. 25: 515-524. 8132491
Kory, N., G.A. Wyant, G. Prakash, J. Uit de Bos, F. Bottanelli, M.E. Pacold, S.H. Chan, C.A. Lewis, T. Wang, H.R. Keys, Y.E. Guo, and D.M. Sabatini. (2018). SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. Science 362:. 30442778
Mon, E.E., F.Y. Wei, R.N.R. Ahmad, T. Yamamoto, T. Moroishi, and K. Tomizawa. (2019). Regulation of mitochondrial iron homeostasis by sideroflexin 2. J. Physiol. Sci 69: 359-373. 30570704
Schmidt, R.S., J.P. Macêdo, M.E. Steinmann, A.G. Salgado, P. Bütikofer, E. Sigel, D. Rentsch, and P. Mäser. (2018). Transporters of Trypanosoma brucei-phylogeny, physiology, pharmacology. FEBS J. 285: 1012-1023. 29063677