Cardiolipin biosynthesis and remodelling in Drosophila melanogaster

Cardiolipin is the signature phospholipid of the inner mitochondrial membrane, where it supports respiratory chain complexes and cristae structure. It is made in mitochondria from CDP-diacylglycerol: Pgs1 forms phosphatidylglycerol phosphate, the phosphatase Ptpmt1 dephosphorylates it to phosphatidylglycerol, and cardiolipin synthase (Cls) joins phosphatidylglycerol with a second CDP-diacylglycerol to make nascent cardiolipin. Nascent cardiolipin is then remodelled: a lipase removes an acyl chain to form monolysocardiolipin, and the transacylase tafazzin (Taz) transfers an acyl chain from another phospholipid to monolysocardiolipin, giving cardiolipin its mature acyl composition. ABHD18 deacylates cardiolipin in flies and mice, and the calcium-independent phospholipase A2 iPLA2-VIA has also been implicated in cardiolipin deacylation. Loss of tafazzin causes monolysocardiolipin to accumulate and models Barth syndrome in flies.

MODULE:dmel_cardiolipin_biosynthesis_remodelingDRAFTCONCRETEMetabolic Pathwaymodules/dmel_cardiolipin_biosynthesis_remodeling.yaml
cardiolipin biosynthetic processGO:0032049 cardiolipin acyl-chain remodelingGO:0035965
FB:FBgg0002238
FlyBase gene group CARLIPB: Cardiolipin biosynthesis and remodelling
FlyBase release FB2026_03 groups 6 D. melanogaster genes as cardiolipin biosynthesis and remodelling (CARLIPB); this module models that group.
GO:0032049
cardiolipin biosynthetic process
GO term grounding the module as cardiolipin biosynthetic process.
GO:0035965
cardiolipin acyl-chain remodeling
GO term grounding the module as cardiolipin acyl-chain remodeling.
PMID:40378955
ABHD18 degrades cardiolipin by stepwise hydrolysis of fatty acids.
Shows that ABHD18 is a cardiolipin lipase in mice and flies and that its inactivation in Drosophila raises cardiolipin and suppresses deacylated cardiolipin accumulation in tafazzin-deficient flies.
Our data demonstrate that ABHD18 is the elusive lipase that hydrolyzes CL in mice and flies and presumably in other organisms.

Boundary. The module covers the six FlyBase members. CDP-diacylglycerol synthesis (CdsA) is upstream context. No GO molecular function term specifically describes tafazzin transacylase activity or ABHD18 cardiolipin deacylase activity, so these are left unassigned. FlyBase groups realized by this module: CARLIPB (FBgg0002238). 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_cardiolipin_biosynthesis_remodeling.yaml. None of the member genes has a gene review in this repository yet.

6Nodes
5Parts
0Variant Sets
0Variants
6Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_cardiolipin_biosynthesis_remodeling 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.

  • pgp_synthesis → pgp_dephosphorylation [NOT_CHECKED]
  • pgp_dephosphorylation → cardiolipin_synthesis [NOT_CHECKED]
  • cardiolipin_synthesis → cardiolipin_deacylation [NOT_CHECKED]
  • cardiolipin_deacylation → cardiolipin_transacylation [NOT_CHECKED]

Function consistency and core coverage

0 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (4 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
pgp_synthesis_pgs1 Pgs1
UniProtKB:Q7KSC9
Gene
CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity
GO:0008444
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
pgp_dephosphorylation_ptpmt1 Ptpmt1
UniProtKB:Q86BN8
Gene
phosphatidylglycerophosphatase activity
GO:0008962
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
cardiolipin_synthesis_cls Cls
UniProtKB:Q8MZC4
Gene
cardiolipin synthase (CMP-forming) activity
GO:0043337
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
cardiolipin_deacylation_ipla2_via iPLA2-VIA
UniProtKB:Q7KUD4
Gene
A2-type glycerophospholipase activity
GO:0004623
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.

Gene-review completeness (0/6 grounded genes reviewed)

0 complete review(s) · 0 with deep research · 6 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
Pgs1 Q7KSC9 ✗ — —
iPLA2-VIA Q7KUD4 ✗ — —
Ptpmt1 Q86BN8 ✗ — —
Abhd18 Q8IQI5 ✗ — —
Cls Q8MZC4 ✗ — —
Taz Q9V6G5 ✗ — —

Details

Context
Drosophila melanogasterNCBITaxon:7227
mitochondrial inner membraneGO:0005743
Cardiolipin biosynthesis and remodellingMetabolic Pathwaydmel_cardiolipin_biosynthesis_remodeling

Mitochondrial cardiolipin synthesis (Pgs1, Ptpmt1, Cls) followed by deacylation-reacylation remodelling (Abhd18, iPLA2-VIA, Taz).

cardiolipin biosynthetic processGO:0032049 cardiolipin acyl-chain remodelingGO:0035965
Context
Drosophila melanogasterNCBITaxon:7227
mitochondrial inner membraneGO:0005743

Connections

PGP made by Pgs1 is dephosphorylated by Ptpmt1.
Phosphatidylglycerol is the substrate of cardiolipin synthase.
Nascent cardiolipin is deacylated to monolysocardiolipin.
Monolysocardiolipin is reacylated by tafazzin.
Part 1: CDP-diacylglycerol + glycerol 3-phosphate to PGP
Phosphatidylglycerol phosphate synthesisMetabolic Pathwaypgp_synthesis

Annotons

Pgs1 Phosphatidylglycerol phosphate synthesis
pgp_synthesis_pgs1
Participant: Gene Product: Pgs1
Gene Product:

Function

CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activityGO:0008444
Part 2: PGP to phosphatidylglycerol
Phosphatidylglycerol phosphate dephosphorylationMetabolic Pathwaypgp_dephosphorylation

Annotons

Ptpmt1 Phosphatidylglycerol phosphate dephosphorylation
pgp_dephosphorylation_ptpmt1
Participant: Gene Product: Ptpmt1
Gene Product:

Function

phosphatidylglycerophosphatase activityGO:0008962
Part 3: phosphatidylglycerol + CDP-diacylglycerol to nascent cardiolipin
Cardiolipin synthesisMetabolic Pathwaycardiolipin_synthesis

Annotons

Cls Cardiolipin synthesis
cardiolipin_synthesis_cls
Participant: Gene Product: Cls
Gene Product:

Function

cardiolipin synthase (CMP-forming) activityGO:0043337
Part 4: cardiolipin to monolysocardiolipin
Cardiolipin deacylationMetabolic Pathwaycardiolipin_deacylation

Abhd18 hydrolyses acyl chains from cardiolipin (its loss raises cardiolipin and lowers deacylated species in tafazzin-deficient flies); iPLA2-VIA is a calcium-independent A2 phospholipase also implicated in cardiolipin deacylation.

Annotons

Abhd18 Cardiolipin deacylation
cardiolipin_deacylation_abhd18
Participant: Gene Product: Abhd18
Gene Product:
iPLA2-VIA Cardiolipin deacylation
cardiolipin_deacylation_ipla2_via
Participant: Gene Product: iPLA2-VIA
Gene Product:

Function

A2-type glycerophospholipase activityGO:0004623
Part 5: monolysocardiolipin to mature cardiolipin
Monolysocardiolipin transacylationMetabolic Pathwaycardiolipin_transacylation

Tafazzin transfers an acyl chain from another phospholipid to monolysocardiolipin.

Annotons

Taz Monolysocardiolipin transacylation
cardiolipin_transacylation_taz
Participant: Gene Product: Taz
Gene Product: