Mitochondrial cofactor/coenzyme carriers (SLC25A19 ThPP, SLC25A26 SAM, SLC25A32 FAD, SLC25A42 CoA)

Many essential enzyme cofactors and coenzymes are synthesised (wholly or partly) in the cytosol but are required by enzymes inside the mitochondrial matrix, which the inner membrane keeps impermeable. A set of SLC25 mitochondrial-carrier proteins solves this by importing specific cofactors into the matrix. This module groups the human cofactor/coenzyme carriers. SLC25A19 imports thiamine pyrophosphate (ThPP), the cofactor of the matrix 2-oxo-acid dehydrogenases (pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase) and transketolase-like enzymes; SLC25A26 is the only carrier that imports S-adenosylmethionine (SAM), the methyl donor for matrix methyltransferases (mtDNA/RNA methylation and cofactor maturation), exchanging it for the product S-adenosylhomocysteine; SLC25A32 imports FAD (and is linked to mitochondrial folate/one-carbon metabolism); and SLC25A42 imports coenzyme A (CoA), needed for matrix acyl-CoA metabolism (fatty-acid oxidation and the TCA cycle), in exchange for intramitochondrial adenine nucleotides. Loss-of-function of these carriers causes cofactor-specific mitochondrial diseases: SLC25A19 — Amish lethal microcephaly and bilateral striatal necrosis/polyneuropathy (THMD3/4); SLC25A26 — combined oxidative phosphorylation deficiency 28; SLC25A32 — riboflavin/folate-responsive exercise intolerance and myopathy; SLC25A42 — a mitochondrial myopathy with episodic metabolic crises.

MODULE:mitochondrial_cofactor_carriersDRAFTMetabolic Pathwaymodules/mitochondrial_cofactor_carriers.yaml
thiamine pyrophosphate transmembrane transportGO:0030974 mitochondrial S-adenosyl-L-methionine transmembrane transportGO:1990543 mitochondrial FAD transmembrane transportGO:1990548 mitochondrial coenzyme A transmembrane transportGO:1990559
GO:0030974
thiamine pyrophosphate transmembrane transport
SLC25A19 mediates thiamine pyrophosphate transmembrane transport (GO:0030974) into the matrix.
GO:1990543
mitochondrial S-adenosyl-L-methionine transmembrane transport
SLC25A26 mediates mitochondrial S-adenosyl-L-methionine transmembrane transport (GO:1990543).
GO:1990548
mitochondrial FAD transmembrane transport
SLC25A32 mediates mitochondrial FAD transmembrane transport (GO:1990548).
GO:1990559
mitochondrial coenzyme A transmembrane transport
SLC25A42 mediates mitochondrial coenzyme A transmembrane transport (GO:1990559).
file:human/SLC25A19/SLC25A19-ai-review.yaml
SLC25A19 gene review (human)
The thiamine pyrophosphate carrier (UniProtKB:Q9HC21, GO:0090422) matches the completed human SLC25A19 review.
file:human/SLC25A26/SLC25A26-ai-review.yaml
SLC25A26 gene review (human)
The S-adenosylmethionine carrier (UniProtKB:Q70HW3, GO:0000095) matches the completed human SLC25A26 review.
file:human/SLC25A32/SLC25A32-ai-review.yaml
SLC25A32 gene review (human)
The FAD carrier (UniProtKB:Q9H2D1, GO:0015230) matches the completed human SLC25A32 review.
file:human/SLC25A42/SLC25A42-ai-review.yaml
SLC25A42 gene review (human)
The coenzyme A carrier (UniProtKB:Q86VD7, GO:0015228) matches the completed human SLC25A42 review.
2Nodes
1Parts
0Variant Sets
0Variants
4Annotons
0Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:mitochondrial_cofactor_carriers deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (4/4 grounded genes reviewed)

4 complete review(s) · 0 with deep research · 0 missing review · 4 reviewed but lacking deep research

Gene Review Complete Deep research
SLC25A19 Q9HC21 ✓ ✓ ✗
SLC25A26 Q70HW3 ✓ ✓ ✗
SLC25A32 Q9H2D1 ✓ ✓ ✗
SLC25A42 Q86VD7 ✓ ✓ ✗

Details

Context
mitochondrial inner membraneGO:0005743
Mitochondrial cofactor/coenzyme carriersMetabolic Pathwaymitochondrial_cofactor_carriers
thiamine pyrophosphate transmembrane transportGO:0030974 mitochondrial S-adenosyl-L-methionine transmembrane transportGO:1990543 mitochondrial FAD transmembrane transportGO:1990548 mitochondrial coenzyme A transmembrane transportGO:1990559
Context
mitochondrial inner membraneGO:0005743

Mitochondrial cofactor/coenzyme import carriers of the SLC25 family, grounded to the completed human gene reviews: SLC25A19 (Q9HC21, GO:0090422 thiamine pyrophosphate transporter — its old deoxynucleotide-carrier identity is refuted, recorded as NOT annotations in the gene review), SLC25A26 (Q70HW3, GO:0000095 SAM transporter / GO:0180003 SAM:SAH antiporter), SLC25A32 (Q9H2D1, GO:0015230 FAD transporter — the primary substrate is FAD per mouse genetics, with folate handling now understood as an indirect FAD-dependent effect; historical folate-transporter terms kept non-core), and SLC25A42 (Q86VD7, GO:0015228 CoA transporter). All are inner-membrane transporters (no catalytic MF). Grouped as parallel, independent cofactor-import carriers (no metabolic connection between them). GO term ids/labels verified against the local go.db (note GO:0051181 "cofactor transport" is obsolete, so the specific per-cofactor transport BPs are used as concepts). These carriers supply cofactors to matrix pathways curated elsewhere (2-oxo-acid dehydrogenases, one-carbon metabolism, fatty-acid oxidation, TCA cycle). Disorders: SLC25A19 — Amish lethal microcephaly / THMD3-4; SLC25A26 — COXPD28; SLC25A32 — riboflavin/folate-responsive myopathy; SLC25A42 — mitochondrial myopathy with metabolic crises.

Part 1: mitochondrial cofactor/coenzyme import carriers
Mitochondrial cofactor/coenzyme carriersReactioncofactor_carriers

Annotons

SLC25A19: thiamine pyrophosphate (ThPP) carrier
slc25a19_activity
Participant: Family: SLC25A19 / thiamine-pyrophosphate carrier family
Family:
SLC25A19 / thiamine-pyrophosphate carrier familyPANTHER:PTHR24089
Representative Members: SLC25A19 (human)UniProtKB:Q9HC21

Function

thiamine pyrophosphate transmembrane transporter activityGO:0090422
Substrates: thiamine pyrophosphate (cytosolic)
Products: thiamine pyrophosphate (matrix)

Locations

mitochondrial inner membraneGO:0005743

Imports thiamine pyrophosphate into the matrix.

SLC25A26: S-adenosylmethionine (SAM) carrier
slc25a26_activity
Participant: Family: SLC25A26 / S-adenosylmethionine carrier family
Family:
SLC25A26 / S-adenosylmethionine carrier familyPANTHER:PTHR45667
Representative Members: SLC25A26 (human)UniProtKB:Q70HW3

Function

S-adenosyl-L-methionine transmembrane transporter activityGO:0000095
Substrates: S-adenosyl-L-methionine (cytosolic) S-adenosyl-L-homocysteine (matrix)
Products: S-adenosyl-L-methionine (matrix, methyl donor) S-adenosyl-L-homocysteine (cytosolic)

Locations

mitochondrial inner membraneGO:0005743

Imports SAM in exchange for matrix SAH.

SLC25A32: FAD (and folate) carrier
slc25a32_activity
Participant: Family: SLC25A32 / FAD-folate mitochondrial carrier family
Family:
SLC25A32 / FAD-folate mitochondrial carrier familyPANTHER:PTHR45683
Representative Members: SLC25A32 (human)UniProtKB:Q9H2D1

Function

FAD transmembrane transporter activityGO:0015230
Substrates: FAD (cytosolic)
Products: FAD (matrix)

Locations

mitochondrial inner membraneGO:0005743

Imports FAD (and links to mitochondrial folate metabolism).

SLC25A42: coenzyme A (CoA) carrier
slc25a42_activity
Participant: Family: SLC25A42 / coenzyme-A carrier family
Family:
SLC25A42 / coenzyme-A carrier familyPANTHER:PTHR24089
Representative Members: SLC25A42 (human)UniProtKB:Q86VD7

Function

coenzyme A transmembrane transporter activityGO:0015228
Substrates: coenzyme A (cytosolic) intramitochondrial adenine nucleotide (e.g. ADP)
Products: coenzyme A (matrix, for acyl-CoA metabolism) adenine nucleotide (cytosolic)

Locations

mitochondrial inner membraneGO:0005743

Imports coenzyme A in exchange for matrix adenine nucleotides.