Citrate-malate shuttle in Drosophila melanogaster

The citrate-malate shuttle moves acetyl units from mitochondria to the cytosol for fatty acid and sterol synthesis and for histone acetylation. Citrate made in the mitochondrial matrix is exported by the mitochondrial citrate carrier, encoded in Drosophila by scheggia (sea), in exchange for malate. In the cytosol ATP-citrate lyase (Acly) cleaves citrate into acetyl-CoA and oxaloacetate, and cytosolic malate dehydrogenase (Mdh1) reduces the oxaloacetate to malate, which can return to the mitochondria through the citrate carrier or be decarboxylated by malic enzyme.

MODULE:dmel_citrate_malate_shuttleDRAFTCONCRETEMetabolic Pathwaymodules/dmel_citrate_malate_shuttle.yaml
mitochondrial citrate transmembrane transportGO:0006843
FB:FBgg0002242
FlyBase gene group CIMALSH: Citrate-malate shuttle
FlyBase release FB2026_03 groups 3 D. melanogaster genes as citrate-malate shuttle (CIMALSH); this module models that group.
GO:0006843
mitochondrial citrate transmembrane transport
GO term grounding the module as mitochondrial citrate transmembrane transport.

Boundary. The module covers the three FlyBase members. Mitochondrial citrate synthase and the cytosolic NADP-malic enzymes (see the cytosolic NADPH regeneration module) are adjacent steps and not parts. The citrate carrier function of Sea and the enzyme functions are assigned by orthology to the conserved mammalian proteins. The module is grounded to mitochondrial citrate transmembrane transport because the newer GO term citrate-malate shuttle (GO:7770108) is not yet in the ontology release used for validation; it should replace the concept once available. FlyBase groups realized by this module: CIMALSH (FBgg0002242). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_citrate_malate_shuttle.yaml. Member genes with a gene review in this repository: Acly, Mdh1, sea.

4Nodes
3Parts
0Variant Sets
0Variants
3Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_citrate_malate_shuttle 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.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • citrate_export → citrate_cleavage [NOT_CHECKED]
  • citrate_cleavage → oxaloacetate_reduction [NOT_CHECKED]

Function consistency and core coverage

3 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (3 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
citrate_export_sea sea
UniProtKB:Q7KSQ0
Gene
citrate transmembrane transporter activity
GO:0015137
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
citrate_cleavage_acly Acly
UniProtKB:A0A0B4LFH8
Gene
ATP citrate synthase activity
GO:0003878
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oxaloacetate_reduction_mdh1 Mdh1
UniProtKB:Q9VKX2
Gene
L-malate dehydrogenase (NAD+) activity
GO:0030060
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).

Gene-review completeness (3/3 grounded genes reviewed)

2 complete review(s) · 3 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
Acly A0A0B4LFH8 ✓ ✓ ✓
Mdh1 Q9VKX2 ✓ 21/22 ✓
sea Q7KSQ0 ✓ ✓ ✓

Details

Context
Drosophila melanogasterNCBITaxon:7227
Citrate-malate shuttleMetabolic Pathwaydmel_citrate_malate_shuttle

Mitochondrial citrate export by Sea, cytosolic citrate cleavage by Acly and oxaloacetate reduction by Mdh1.

mitochondrial citrate transmembrane transportGO:0006843
Context
Drosophila melanogasterNCBITaxon:7227

Connections

Exported citrate is cleaved by ATP-citrate lyase in the cytosol.
Oxaloacetate from citrate cleavage is reduced to malate by Mdh1.
oxaloacetate_reduction -> citrate_export Provides Input For
Cytosolic malate is the counter-substrate for citrate export.
Part 1: citrate export from mitochondria in exchange for malate
Mitochondrial citrate exportMetabolic Pathwaycitrate_export

Annotons

sea Mitochondrial citrate export
citrate_export_sea
Participant: Gene Product: sea
Gene Product:

Function

citrate transmembrane transporter activityGO:0015137

Locations

mitochondrial inner membraneGO:0005743
Part 2: citrate to acetyl-CoA + oxaloacetate
Cytosolic citrate cleavageMetabolic Pathwaycitrate_cleavage

Annotons

Acly Cytosolic citrate cleavage
citrate_cleavage_acly
Participant: Gene Product: Acly
Gene Product:

Function

ATP citrate synthase activityGO:0003878

Locations

cytosolGO:0005829
Part 3: oxaloacetate to malate
Oxaloacetate reductionMetabolic Pathwayoxaloacetate_reduction

Annotons

Mdh1 Oxaloacetate reduction
oxaloacetate_reduction_mdh1
Participant: Gene Product: Mdh1
Gene Product:

Function

L-malate dehydrogenase (NAD+) activityGO:0030060

Locations

cytosolGO:0005829