CG4598

Gene Description

CG4598 is one of a tandem cluster of three Drosophila melanogaster mitochondrial enoyl-CoA delta isomerase 1 paralogs (with CG4592 and CG4594), the mitochondrial-type (human ECI1 class) delta(3),delta(2)-enoyl-CoA isomerases (EC 5.3.3.8). It is an auxiliary enzyme of unsaturated fatty acid beta-oxidation that isomerizes both 3-cis (3Z) and 3-trans (3E) enoyl-CoA double bonds into the 2-trans (2E) form (with a preference for (3Z)-enoyl-CoAs), regenerating the substrate of the core enoyl-CoA hydratase so that unsaturated fatty acids with double bonds at odd-numbered positions can be fully degraded. It localizes to the mitochondrial matrix (also supported by organelle proteomics) and, unlike the peroxisomal-type isomerase Dci, is a mitochondrial isomerase relevant to the mitochondrial unsaturated-FAO cassette. Of the three tandem paralogs, CG4598 uniquely has direct organelle-proteomics localization support (HDA mitochondrion, PMID:19317464).

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetically inferred mitochondrial localization, consistent with the mitochondrial ECI1 family; less specific than the mitochondrial matrix. Reason: Correct compartment; the mitochondrial matrix (GO:0005759) is the core location.
GO:0006635 fatty acid beta-oxidation	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred participation in fatty acid beta-oxidation - the auxiliary delta(3),delta(2)-enoyl-CoA isomerase step for unsaturated fatty acids. Reason: Core biological process for this auxiliary isomerase of (unsaturated) fatty acid beta-oxidation.
GO:0004165 delta(3)-delta(2)-enoyl-CoA isomerase activity	IEA GO_REF:0000003	ACCEPT	Summary: EC-based electronic assignment of delta(3),delta(2)-enoyl-CoA isomerase activity (EC 5.3.3.8) - the defining molecular function of this mitochondrial ECI1-class isomerase. Reason: Core molecular function; concordant with the UniProt name and mitochondrial ECI1 family membership. Supporting Evidence: file:DROME/CG4598/CG4598-uniprot.txt Enoyl-CoA delta isomerase 1, mitochondrial
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: Electronic (UniProt subcellular-location) annotation to the mitochondrial matrix - the correct, specific compartment for this mitochondrial-type enoyl-CoA isomerase. Reason: The specific, core location; distinguishes CG4598 from the peroxisomal-type isomerase Dci. Supporting Evidence: file:DROME/CG4598/CG4598-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0004165 delta(3)-delta(2)-enoyl-CoA isomerase activity	ISS GO_REF:0000024	ACCEPT	Summary: Orthology-based delta(3),delta(2)-enoyl-CoA isomerase activity, duplicating the core molecular-function call. Reason: Core molecular function of CG4598. Supporting Evidence: file:DROME/CG4598/CG4598-uniprot.txt Enoyl-CoA delta isomerase 1, mitochondrial
GO:0005739 mitochondrion	HDA PMID:19317464 Mapping organelle proteins and protein complexes in Drosophi...	KEEP AS NON CORE	Summary: High-throughput organelle-proteomics localization to the mitochondrion, corroborating the mitochondrial-matrix assignment. Reason: Correct compartment from proteomics; the mitochondrial matrix is the specific core location.

Core Functions

Mitochondrial delta(3),delta(2)-enoyl-CoA isomerase (EC 5.3.3.8): isomerizes 3Z/3E-enoyl-CoA to 2E-enoyl-CoA, the auxiliary step that lets unsaturated fatty acids with odd-position double bonds re-enter the beta-oxidation spiral. One of three fly mitochondrial ECI1 paralogs (CG4592/CG4594/CG4598).

Molecular Function:

delta(3)-delta(2)-enoyl-CoA isomerase activity

Directly Involved In:

fatty acid beta-oxidation

Cellular Locations:

mitochondrial matrix

Supporting Evidence:

file:DROME/CG4598/CG4598-uniprot.txt
Key enzyme of fatty acid beta-oxidation.

References

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Suggested Experiments

Experiment: Expression profiling and individual/combined knockouts of CG4592, CG4594 and CG4598 to test functional redundancy and confirm the mitochondrial delta(3),delta(2)-enoyl-CoA isomerase step of unsaturated fatty acid beta-oxidation in the fly.

Hypothesis: The CG4592/CG4594/CG4598 cluster provides the mitochondrial delta(3),delta(2)-enoyl-CoA isomerase activity (distinct from peroxisomal Dci) required for the mitochondrial unsaturated-FAO cassette.