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    Mitochondrial Carriers

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    Definition

    Mitochondrial carriers play a fundamental role in cellular metabolism, connecting mitochondrial with cytosolic reactions. By transporting substrates across the inner membrane of mitochondria, they contribute to many processes that are central to cellular function. The genome of Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family, most of which have been functionally characterized.

    1. Introduction

    Mitochondria are subcellular organelles involved in different pathways. In addition to supplying energy, mitochondria contribute to many processes that are central to cellular function and that require the exchange of metabolites between the cytosol and the mitochondrial matrix. These organelles are surrounded by a double-membrane system consisting of an outer mitochondrial membrane (OMM) that surrounds the inner membrane (IMM); the two membranes are separated by an intermembrane space. Numerous transport processes occur between the two mitochondrial membranes. The OMM contains large pores (porins), which are large enough to allow the passage of ions and molecules as large as a small protein. The IMM is highly impermeable and, therefore, is characterized by the presence of specific carrier proteins which transport metabolites inside the mitochondria. These proteins, which are encoded by nuclear DNA, play a fundamental role in cellular metabolism since they connect the intra-mitochondrial reactions with the extra-mitochondrial (cytosolic) ones.
    Mitochondrial carriers are widespread in all eukaryotes and considerable research has been conducted on characterizing the members of the mitochondrial carrier family (MCF) in yeast, mammals, plant, and insects. In particular, in Saccharomyces cerevisiae, 35 members of the MCF have been identified and, in large part, functionally characterized ( Table 1 ).

    Table 1. List of mitochondrial carriers from Saccharomyces cerevisiae. Alternative carrier names are in brackets.

    Carrier

     

    Substrates Transported

    Function/Metabolic Pathway

    ADP/ATP carrier

    Aac1p

    Aac2p

    Aac3p

    ADP, ATP

    Oxidative phosphorylation

    ADP/ATP carrier (peroxisomal)

    Ant1p

    ATP, AMP

    Lipid metabolism

    Adenosine 5′-phosphosulfate carrier

    Apsc1p

    Adenosine 5’-phosphosulfate 3’-phospho-adenosine 5’-phosphosulfate, sulfate, and phosphate

    Thermotolerance and synthesis of methionine and glutathione at elevated temperatures

    ATP-Mg/phosphate carrier

    Sal1p

    ADP, ATP, ATP-Mg, and Pi (Ca2+-stimulated)

    Glucose-induced calcium signal

    Aspartate/glutamate carrier

    Agc1p

    Ymc1p

    Ymc2p

     

    Aspartate, glutamate

    Nitrogen metabolism and ornithine synthesis

    Malate-aspartate NADH shuttle

    Carnitine carrier

    Crc1p

    Carnitine, acetyl-carnitine, and propionyl-carnitine (medium- and long-chain acyl-carnitines less efficiently)

    Lipid metabolism

    Citrate carrier

    Ctp1p

    Citrate, tricarboxylates

    Lipid and glucose metabolism

    Citrate/oxoglutarate carrier

    Yhm2p

    (Coc1p)

    Citrate, oxoglutarate (oxaloacetate, succinate, and fumarate less efficiently)

    Increase in the NADPH reducing power in the cytosol

    Component of the citrate-oxoglutarate NADPH redox shuttle

    Coenzyme A carrier

    Leu5p

    Coenzyme A

    Distribution of Coenzyme A

    Dicarboxylate carrier

    Dic1p

    Dicarboxylates (malate, succinate, or malonate), Pi, sulfate, and thiosulfate

    Anaplerotic role for the Krebs cycle

    FAD carrier

    Flx1p

    FAD

    Flavin transport

    GTP/GDP carrier

    Ggc1p

    GTP, GDP, dGTP, dGDP, and the structurally related ITP and IDP (guanosine 5′-tetraphosphate and the (deoxy)nucleoside di- and triphosphates of U and T less efficiently)

    Protein synthesis and RNA synthesis

    Magnesium carrier

    Mme1

    Magnesium

    Homeostasis of magnesium

    NAD+ carrier

    Ndt1p

    Ndt2p

    NAD+ (dAMP and dGMP, NADH, NADP+, or NADPH less efficiently)

    Import NAD+ into mitochondria

    Iron carrier

    Mrs3p

    Mrs4p

    Iron

    Iron accumulation

    Ornithine carrier

    Ort1p

    Ornithine/H+ or ornithine/ornithine (arginine and lysine less efficiently)

    Arginine synthesis

    Oxaloacetate carrier

    Oac1p

    Oxaloacetate, sulfate, and a-isopropylmalate (various substrates of the dicarboxylate and oxoglutarate carriers less efficiently)

    Anaplerotic role for the Krebs cycle

    Leucine synthesis

    Oxodicarboxylate carrier

    Odc1p

    Odc2p

    Oxoadipate, oxoglutarate (dicarboxylates and malate less efficiently)

    Nitrogen assimilation

    Malate/aspartate shuttle

    Phosphate carrier

    Mir1p

    Pic2p

    Phosphate

    Oxidative phosphorylation

    Pyridoxal 5’-phosphate transporter

    Mtm1p

    Pyridoxal 5’-phosphate transporter

    Pyridoxal 5’-phosphate trafficking

    Iron homeostasis

    Pyrimidine nucleotide carrier

    Pyt1p

    (Rim2p)

    Pyrimidine (deoxy)nucleoside mono-, di- and triphosphates

    mtDNA and mtRNA synthesis

    S-adenosylmethionine carrier

    Sam5p

    S-adenosylmethionine

    Biosynthesis of biotin and lipoic acid

    Methylation reactions of mtDNA, mtRNA, and mitochondrial proteins

    Succinate/fumarate carrier

    Sfc1p

    Succinate, fumarate

    Gluconeogenesis

    Thiamine pyrophosphate carrier

    Tpc1p

    Thiamine pyrophosphate, thiamine monophosphate ((deoxy)nucleotides less efficiently)

    Branched chain amino acids synthesis

     

    Ugo1p

     

    Mitochondrial fusion

     

    YDL119c

    (Hem25)

    Glicine

    Heme synthesis

     

    YFR045w product

    ?

    ?

    With a single exception, these proteins are found in the inner membranes of mitochondria. By transporting several substrates across this membrane, they are indirectly involved in many biochemical processes, such oxidative phosphorylation (OXPHOS) ( Figure 1 ), the transfer of reducing equivalents ( Figure 2 ), the transport of Krebs cycle intermediates ( Figure 3 ), fatty acid metabolism ( Figure 4 ), gluconeogenesis (Figure 5), and amino acid synthesis ( Figure 6 ).

    This entry is adapted from 10.3390/ijms22168496