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)



This family belongs to the .

 

References:

Azzi, A., M. Glerum, R. Koller, W. Mertens and S. Spycher (1993). The mitochondrial tricarboxylate carrier. J. Bioenerg. Biomembr. 25: 515-524.

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:.

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.

Examples:

TC#NameOrganismal TypeExample
2.A.54.1.1

Mitochondrial serine (and possibly cystine and alanine) carrier, Sideroflexin-1 (SFXN1) of 322 aas and possibly 6 TMSs (Kory et al. 2018). This system is required for one-carbon metabolism because serine is converted inot glycine and formate in the mitochondrion. 

Eukaryotes

MTC of Homo sapiens

 
2.A.54.1.2Hypothetical 36.7 KDa protein AH6.2 Eukaryotes AH6.2 of Caenorhabditis elegans
 
2.A.54.1.3

Sideroflexin-4 (Breast cancer resistance marker 1)

Animals

Sideroflexin-4 of Homo sapiens

 
2.A.54.1.4Probable mitochondrial transport protein FSF1 (Fungal sideroflexin-1)FungiFSF1 of Saccharomyces cerevisiae
 
2.A.54.1.5Sideroflexin-5AnimalsSfxn5 of Mus musculus
 
2.A.54.1.6Sideroflexin-3AnimalsSfxn3 of Mus musculus
 
2.A.54.1.7

Tricarboxylic acid (TCA) transporter of 327 aas and 6 TMSs. Found to be essential for bloodstream-form Trypanosoma brucei through a genome-wide RNAi screen (Schmidt et al. 2018).

TCA carrier of Trypanosoma brucei