SLC25A1 may exchange mitochondrial PEP for cytosolic anion

Stable Identifier
Reaction [transition]
Homo sapiens
phosphoenolpyruvate [mitochondrial matrix] + citrate [cytosol] => phosphoenolpyruvate [cytosol] + citrate [mitochondrial matrix]
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A variety of models assign phosphoenolpyruvate (PEP) generated in the mitochondrial matrix by PCK2 (Phosphoenolpyruvate carboxykinase (GTP), mitochondrial) a role in the regulation of gluconeogenesis and its integration with other aspects of metabolism (e.g., Bluemel et al. 2021; Merrins et al. 2022; Soling et al. 1973; Yu et al. 2021). An attractive recent suggestion is that this process may specifically play a key role in regulating insulin secretion by pancreatic beta cells in response to changing blood glucose levels (Merrins et al. 2022).

Exchange of citrate for PEP across a membrane has been demonstrated in several model systems (Kleineke et al. 1973; Robinson 1971; Shug & Shrago 1973; Sul et al. 1976; Stipani et al, 1980) but the direction in which it proceeds under physiological conditions and the identity of the protein or proteins that enable this exchange remain unclear, although the citrate transporter SLC25A1 has been identified as a candidate.

Here, this hypothetical reaction is annotated as the exchange of mitochondrial PEP for an unspecified cytosolic anion, A-, possibly mediated by SLC25A1.

Literature References
PubMed ID Title Journal Year
11945784 Transport of phosphoenolpyruvate by the tricarboxylate transporting system in mammalian mitochondria

Robinson, BH

FEBS Lett 1971
7470147 Citrate transport in liposomes reconstituted with triton extracts from mitochondria

Krämer, R, Stipani, I, Palmieri, F, Klingenberg, M

Biochem Biophys Res Commun 1980
4745729 Relationship between intracellular distribution of phosphoenolpyruvate carboxykinase, regulation of gluconeogenesis, and energy cost of glucose formation

Janson, G, Kleineke, J, Söling, HD, Willms, B, Kuhn, A

Eur J Biochem 1973
11946196 Effects of synthetic analogues of phosphoenolpyruvate on muscle and liver pyruvate kinase, muscle enolase, liver phosphoenolpyruvate carboxykinase and on the intra-/extra-mitochondrial tricarboxylic acid carrier transport system

Kleineke, J, Söling, HD, Walter, U, Sauer, H

FEBS Lett 1971
34520823 PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells

Hrzenjak, A, Haitzmann, T, Fendt, SM, Madreiter-Sokolowski, CT, Planque, M, Olschewski, H, Graier, WF, Leithner, K, Bluemel, G

Free Radic Biol Med 2021
35728586 Metabolic cycles and signals for insulin secretion

Kibbey, RG, Prentki, M, Merrins, MJ, Corkey, BE

Cell Metab 2022
4716993 Inhibition of phosphoenolpyruvate transport via the tricarboxylate and adenine nucleotide carrier systems of rat liver mitochondria

Shrago, E, Shug, AL

Biochem Biophys Res Commun 1973
1252077 Relationship of phosphoenolpyruvate transport, acyl coenzyme A inhibition of adenine nucleotide translocase and calcium ion efflux in guinea pig heart mitochondria

Shug, AL, Shrago, E, Sul, HS

Arch Biochem Biophys 1976
4719206 On the specificity of the tricarboxylate carrier system in rat liver mitochondria

Kleineke, J, Söling, HD, Sauer, H

FEBS Lett 1973
34020084 Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis

Meng, S, Ma, H, Xiang, M, Yu, S

Mol Metab 2021
Catalyst Activity

tricarboxylic acid transmembrane transporter activity of SLC25A1 [mitochondrial inner membrane]

Orthologous Events
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