Evidence map›Paper›PMID 41603375›Full record

ArticleCardiovascular research2026

Mitochondrial succinate transport is required for cardiac ischaemia/reperfusion injury.

Laura Pala, María Torres-López, Stuart T Caldwell, Joyce Valadares, Emily M Smith, Katherine L Hammond, Olga Sauchanka, Jiro Abe, Thomas Krieg, Richard C Hartley and 2 more

Abstract read
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In one paragraph

Article in Cardiovascular research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Laura PalaSchool of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK.
María Torres-LópezInstitute of Biomedicine of Seville (IBiS), Hospital 'Universitario Virgen del Rocío'/CSIC/University of Seville, Seville 41013, Spain.
Stuart T CaldwellSchool of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK.
Joyce ValadaresMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Emily M SmithMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Katherine L HammondMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Olga SauchankaDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Jiro AbeMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Thomas KriegDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.ORCID 0000-0002-5192-580X
Richard C HartleySchool of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK.
Michael P MurphyMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Hiran A PragMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.ORCID 0000-0002-4753-8567

Funding

British Heart Foundation PG/23/11344Medical Research CouncilRoyal Society Research RGS\R2\252037University of Glasgow studentshipWellcome Trust Investigator 110158/Z/15/ZWellcome Trust Investigator 220257/B/20/ZWellcome Trust Investigator 220257/Z/20/Z
6 · The paper itself

Abstract

aimsSuccinate accumulates significantly during myocardial ischaemia, and its rapid oxidation upon reperfusion is a critical driver of ischaemia/reperfusion (I/R) injury. The transport of succinate across the mitochondrial inner membrane, particularly by the dicarboxylate carrier (DIC; SLC25A10), is hypothesized to play a crucial role in mediating these pathological succinate dynamics. However, tools to test this hypothesis by modulating mitochondrial succinate transport in biological systems are lacking. METHODS AND

resultsC57BL/6J mice, isolated Wistar Rat heart mitochondria, bovine heart mitochondrial membranes, C2C12 mouse myoblasts, and primary adult mouse cardiomyocytes were used as in vitro and in vivo models. Butylmalonate prodrugs were synthesized and tested. Isolated mitochondria were used to assess succinate-dependent respiration and reactive oxygen species (ROS) production. Cells were treated with succinate dehydrogenase (SDH) inhibitors or exposed to anoxia and butylmalonate esters. Mouse hearts were subjected to in vivo left anterior descending coronary artery ligation. Succinate and butylmalonate levels were measured by targeted liquid chromatography-tandem mass spectrometry, and infarct size by TTC (23,5-triphenyl-2H-tetrazolium chloride) staining. Knockdown of DIC, but not of the oxoglutarate carrier OGC, in C2C12 cells prevented succinate accumulation by SDH inhibition and anoxia. The only extant DIC inhibitor butylmalonate, is limited by poor cell permeability. We synthesized diacetoxymethyl butylmalonate (DAB), which efficiently delivers butylmalonate intramitochondrially in isolated heart mitochondria and cells. DAB inhibited succinate-dependent respiration and ROS production. DAB prevented succinate accumulation in cells treated with SDH inhibitors. DAB delivered butylmalonate to cardiac mitochondria when administered to mice in vivo and reduced infarct size by perturbing mitochondrial succinate transport.

conclusionThe DIC is a key node in the cellular distribution of succinate, controlling its transport between mitochondria and the cytosol. These findings highlight the potential of DIC as a promising therapeutic target for conditions where succinate elevation contributes to pathogenesis, such as cardiac I/R injury.

Indexed as

Dicarboxylic Acid TransportersMitochondria, HeartMyocardial InfarctionMyocardial Reperfusion InjuryMyocytes, CardiacSuccinic AcidAnimalsBiological TransportCell LineDisease Models, AnimalMaleMalonatesMembrane Transport ProteinsMiceMice, Inbred C57BLMitochondrial Membrane Transport ProteinsDicarboxylic Acid TransportersMalonatesMembrane Transport ProteinsMitochondrial Membrane Transport Proteinsoxoglutarate translocatorProdrugsReactive Oxygen SpeciesSuccinate DehydrogenaseSuccinic AcidButylmalonateIschaemia/reperfusion injuryMitochondrial dicarboxylate carrierMitochondrial transportMyocardial infarctionSLC25A10Succinate

Identifiers

PMID41603375
PMCPMC13123664

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.