Reactome | SLC25A1 may exchange mitochondrial PEP for cytosolic anion

SLC25A1 may exchange mitochondrial PEP for cytosolic anion

Stable Identifier

R-HSA-372449

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, mitochondrial inner membrane, mitochondrial matrix

Synonyms

phosphoenolpyruvate [mitochondrial matrix] + citrate [cytosol] => phosphoenolpyruvate [cytosol] + citrate [mitochondrial matrix]

ReviewStatus

5/5

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SLC25A1 may exchange mitochondrial PEP for cytosolic anion

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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 Stipani, I, Krämer, R, 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 Söling, HD, Kleineke, J, Willms, B, Janson, G, 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 Söling, HD, Walter, U, Sauer, H, Kleineke, J	FEBS Lett	1971
34520823	PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells Bluemel, G, Planque, M, Madreiter-Sokolowski, CT, Haitzmann, T, Hrzenjak, A, Graier, WF, Fendt, SM, Olschewski, H, Leithner, K	Free Radic Biol Med	2021
35728586	Metabolic cycles and signals for insulin secretion Merrins, MJ, Corkey, BE, Kibbey, RG, Prentki, M	Cell Metab	2022
4716993	Inhibition of phosphoenolpyruvate transport via the tricarboxylate and adenine nucleotide carrier systems of rat liver mitochondria Shug, AL, Shrago, E	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 Sul, HS, Shrago, E, Shug, AL	Arch Biochem Biophys	1976
4719206	On the specificity of the tricarboxylate carrier system in rat liver mitochondria Kleineke, J, Sauer, H, Söling, HD	FEBS Lett	1973
34020084	Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis Yu, S, Meng, S, Xiang, M, Ma, H	Mol Metab	2021