LPD1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity	IBA GO_REF:0000033	ACCEPT	Summary: Dihydrolipoyl dehydrogenase activity inherited from the ancestral E3 node, which is seeded by characterized bacterial, yeast, mammalian and plant LPDs, including the paralog At3g17240. Reason: This is the defining catalytic activity of mtLPD1, the L protein of the glycine decarboxylase complex and the E3 of the mitochondrial 2-oxoacid dehydrogenase complexes. The FAD and NAD binding residues and the redox-active disulfide are conserved. Recombinant Arabidopsis mtLPD1 has been characterized biochemically and is inhibited by its product NADH. Same action as the mtLPD2 review. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + NAD(+) = N(6)-[(R)-lipoyl]-L-lysyl-[protein] + NADH + H(+) PMID:22303256 This reaction is catalyzed by L-protein, a homodimeric dihydrolipoamide dehydrogenase (EC 1.8.1.4). PMID:38518065 biochemical analysis of recombinant mtLPD1 supported this. It also revealed mtLPD1 inhibition by NADH
GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity	IEA GO_REF:0000120	ACCEPT	Summary: Dihydrolipoyl dehydrogenase activity inferred from the InterPro lipoamide dehydrogenase signature and the EC/RHEA mapping. Reason: Consistent with the IBA row, the UniProt catalytic activity and the biochemistry of recombinant mtLPD1. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + NAD(+) = N(6)-[(R)-lipoyl]-L-lysyl-[protein] + NADH + H(+) file:ARATH/mtLPD1/mtLPD1-uniprot.txt InterPro; IPR006258; Lipoamide_DH.
GO:0005507 copper ion binding	HDA PMID:20018591 Divalent metal ions in plant mitochondria and their role in ...	MARK AS OVER ANNOTATED	Summary: Retained on Cu2+-charged immobilized metal affinity chromatography (IMAC) of mitochondrial proteins. Reason: IMAC retention shows surface affinity for an immobilized metal, often through exposed histidine or cysteine residues. It does not show physiological copper binding. LPD is an FAD/NAD flavoprotein with no known metal cofactor. The study surveyed proteins that might suffer metal-catalysed oxidative damage; it did not define metal-binding functions. Same action as the mtLPD2 review. Supporting Evidence: PMID:20018591 Immobilized metal affinity chromatography charged with Cu(2+), Zn(2+), and Co(2+) was used to identify over 100 mitochondrial proteins with metal-binding properties. file:ARATH/mtLPD1/mtLPD1-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
GO:0005524 ATP binding	HDA PMID:17137349 Analysis of the soluble ATP-binding proteome of plant mitoch...	MARK AS OVER ANNOTATED	Summary: Captured on immobilized ATP from the soluble mitochondrial proteome. Reason: ATP-affinity capture also enriches dinucleotide-binding proteins. LPD binds FAD and NAD+ through Rossmann-type folds, which can explain retention on an ATP matrix. ATP is not a known substrate or effector of E3, so ATP binding is not an informative function for this protein. Same action as the mtLPD2 review. Supporting Evidence: PMID:17137349 including 14-3-3 proteins and RNA binding proteins, as well as proteins known to contain nucleotide binding domains
GO:0005634 nucleus	HDA PMID:28887381 Global Analysis of Membrane-associated Protein Oligomerizati...	MARK AS OVER ANNOTATED	Summary: Nucleus assignment from protein correlation profiling of membrane-associated protein complexes. Reason: mtLPD1 is imported into mitochondria by an experimentally verified transit peptide and acts in the matrix, and no targeted study places it in the nucleus. A single high-throughput fractionation hit for a protein localized elsewhere is marked as over-annotated rather than removed, following projects/ARATH/organelle-audit.md. The same paper gave mtLPD2 a cytosol call, which was treated the same way. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005739 mitochondrion	HDA PMID:11743115 Analysis of the Arabidopsis mitochondrial proteome.	ACCEPT	Summary: Identified on 2D gels of Arabidopsis cell-culture mitochondria as the product of AAF34795, the mtLPD1 cDNA, distinguished from mtLPD2 by peptide mass fingerprinting. Reason: Direct, isoform-resolved detection of mtLPD1 in purified mitochondria, consistent with the experimentally determined transit peptide and matrix location. In these non-photosynthetic mitochondria mtLPD2 was the more abundant isoform. Supporting Evidence: PMID:11743115 Two distinct lipoamide dehydrogenase proteins were identified as the products of Q9 M 5K2 and AAF34795 PMID:11743115 This is the first evidence to our knowledge that these two genes are translated to form lipoamide dehydrogenase proteins that accumulate in plant mitochondria.
GO:0005739 mitochondrion	HDA PMID:14671022 Experimental analysis of the Arabidopsis mitochondrial prote...	ACCEPT	Summary: Identified in the LC-MS/MS mitochondrial proteome. UniProt cites this paper for the matrix location. Reason: Consistent with all other localization evidence. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005739 mitochondrion	HDA PMID:17137349 Analysis of the soluble ATP-binding proteome of plant mitoch...	ACCEPT	Summary: Identified in the soluble mitochondrial matrix fraction captured on ATP affinity media. Reason: The protein was found in purified mitochondria, which supports the location regardless of the ATP-binding interpretation. Supporting Evidence: PMID:17137349 A range of highly enriched proteins were identified from the mitochondrial proteome
GO:0005739 mitochondrion	HDA PMID:18385124 Heterogeneity of the mitochondrial proteome for photosynthet...	ACCEPT	Summary: Detected in the shoot and cell-culture mitochondrial proteome comparison, which highlighted the elevated photorespiratory apparatus of shoot mitochondria. Reason: Consistent with the transit peptide and matrix location. Supporting Evidence: PMID:18385124 Combined these data showed the elevated level of the photorespiratory apparatus
GO:0005739 mitochondrion	HDA PMID:22923678 Putative glycosyltransferases and other plant Golgi apparatu...	ACCEPT	Summary: Assigned to mitochondria by LOPIT organelle proteomics. Reason: The LOPIT assignment agrees with the targeted and proteomic evidence. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005739 mitochondrion	HDA PMID:25293756 A proteomic strategy for global analysis of plant protein co...	ACCEPT	Summary: Mitochondrial assignment from a leaf protein-complex proteomics study. Reason: Consistent with all other localization evidence. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Mitochondrial activity location inherited from the eukaryotic mitochondrial E3 node. Reason: mtLPD1 belongs to the mitochondrial E3 clade, not the plastid LPD clade, and carries an experimentally verified mitochondrial transit peptide. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt TRANSIT 1..36
GO:0005739 mitochondrion	ISM GO_REF:0000122	ACCEPT	Summary: Mitochondrial targeting predicted by AtSubP. Reason: The prediction agrees with the experimental evidence. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt TRANSIT 1..36
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: Mitochondrial matrix location from the UniProt subcellular-location mapping. The underlying UniProt statement has experimental evidence. Reason: E3 is a soluble matrix component of the glycine decarboxylase and 2-oxoacid dehydrogenase complexes, and UniProt supports the matrix location with experimental evidence (PubMed 14671022). This is the most specific supported location. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:11598235 once in the mitochondrial matrix, are interchangeable among the different multienzyme complexes
GO:0005794 Golgi apparatus	RCA NOT PMID:22430844 Isolation and proteomic characterization of the Arabidopsis ...	ACCEPT	Summary: The NOT annotation records that the Golgi proteome analysis classified mtLPD1 as a contaminant rather than a Golgi resident. Reason: The negative claim agrees with the established mitochondrial matrix location. The Golgi study explicitly estimated a fraction of contaminating proteins from other compartments. Same action as the mtLPD2 review. Supporting Evidence: PMID:22430844 A composition analysis indicated that approximately 19% of proteins were likely derived from contaminating compartments and ribosomes.
GO:0006103 2-oxoglutarate metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: 2-oxoglutarate metabolism, through the E3 role in the 2-oxoglutarate dehydrogenase complex, inherited from the ancestral E3 node. Reason: The mitochondrial E3 is an obligatory catalytic subunit of the 2-oxoglutarate dehydrogenase complex of the TCA cycle, and the IBA node includes mtLPD1. Although mtLPD1 is the main leaf GDC L protein, its function is described as required for all four mitochondrial lipoyl-dependent complexes, including the TCA cycle one, and mutant analysis shows that the two paralogs overlap in 2-oxoacid dehydrogenase functions. Same action as the mtLPD2 review. Supporting Evidence: PMID:38861078 its function is required to drive four multienzymes involved in photorespiration, the tricarboxylic acid (TCA) cycle, and the degradation of branched-chain amino acids PMID:11598235 This indicates that mtLPD1 can substitute for mtLPD2 and associate with all these multienzyme complexes.
GO:0008270 zinc ion binding	HDA PMID:20018591 Divalent metal ions in plant mitochondria and their role in ...	MARK AS OVER ANNOTATED	Summary: Retained on Zn2+-charged IMAC of mitochondrial proteins. Reason: As for copper, IMAC retention does not establish a physiological zinc-binding function, and LPD has no known zinc site. Same action as the mtLPD2 review. Supporting Evidence: PMID:20018591 Immobilized metal affinity chromatography charged with Cu(2+), Zn(2+), and Co(2+) was used to identify over 100 mitochondrial proteins with metal-binding properties.
GO:0009416 response to light stimulus	IEP PMID:11598235 Characterization of two cDNAs encoding mitochondrial lipoami...	KEEP AS NON CORE	Summary: mtLPD1 mRNA is strongly induced when etiolated seedlings are transferred to light, more than mtLPD2 mRNA. Reason: The expression response is stated directly in the abstract and fits the light-induced expression of the photorespiratory GDC genes. It is a regulatory property of the gene, not part of its molecular function or the process it executes, so it is kept as non-core. Supporting Evidence: PMID:11598235 Analysis of etiolated seedlings transferred to light showed a strong induction of RNA expression for mtLPD1 but only a moderate induction of mtLPD2. PMID:22303256 Most of these genes are strongly light regulated
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	TOO GENERAL	Summary: Generic oxidoreductase activity from pyridine nucleotide-disulfide oxidoreductase InterPro signatures. Reason: This is true, but it is entailed by the accepted GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity, which is_a oxidoreductase activity. Same action as the mtLPD2 review. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
GO:0016668 oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor	IEA GO_REF:0000002	TOO GENERAL	Summary: Oxidoreductase activity on sulfur-group donors with NAD(P) as acceptor, from InterPro. Reason: This is correct, but it is the direct parent of the accepted GO:0004148, which already entails it. Same action as the mtLPD2 review. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + NAD(+) = N(6)-[(R)-lipoyl]-L-lysyl-[protein] + NADH + H(+)
GO:0045252 oxoglutarate dehydrogenase complex	IBA GO_REF:0000033	ACCEPT	Summary: Subunit (E3) of the 2-oxoglutarate dehydrogenase complex, inherited from the mitochondrial E3 node. Reason: The mitochondrial E3 is shared by the 2-oxoacid dehydrogenase complexes and the GDC. There is no Arabidopsis-specific evidence of divergence, the IBA node (mitochondrial eukaryotic E3s) includes mtLPD1, and the authors who proposed the division of labour concluded that mtLPD1 can associate with all these complexes. mtLPD1 mainly serves the leaf GDC, but its OGDC membership is still a real function. Same action as the mtLPD2 review. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt Lipoamide dehydrogenase is a component of the glycine decarboxylase (GDC) or glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. PMID:11598235 This indicates that mtLPD1 can substitute for mtLPD2 and associate with all these multienzyme complexes.
GO:0045271 respiratory chain complex I	IDA PMID:20197505 Internal architecture of mitochondrial complex I from Arabid...	REMOVE	Summary: A lipoamide dehydrogenase spot was found in complex I preparations from Arabidopsis mitochondria. Reason: The authors of the cited paper list lipoamide dehydrogenase among the contaminating proteins of their complex I preparation, not among its subunits. Nothing suggests that E3 is a structural component of NADH:ubiquinone oxidoreductase. The contradiction is stated in the source itself, so this does not second-guess the curator. Same action as the mtLPD2 review. Supporting Evidence: PMID:20197505 a few contaminating proteins like prohibitin, the β-subunit of ATP synthase (complex V), Ser hydroxymethyltransferase, and lipoamide dehydrogenase
GO:0045271 respiratory chain complex I	IEA GO_REF:0000117	REMOVE	Summary: Complex I membership predicted by an ARBA machine-learning rule. Reason: The ARBA rule most likely reflects contaminant-derived complex I annotations of LPDs such as the IDA row above. E3 is a soluble matrix flavoprotein of the 2-oxoacid dehydrogenase and glycine decarboxylase complexes, and the complex I study names it as a contaminant. Same action as the mtLPD2 review. Supporting Evidence: PMID:20197505 a few contaminating proteins like prohibitin, the β-subunit of ATP synthase (complex V), Ser hydroxymethyltransferase, and lipoamide dehydrogenase
GO:0046686 response to cadmium ion	IEP PMID:20005002 Leaf proteome responses of Arabidopsis thaliana exposed to m...	UNDECIDED	Summary: Leaf 2D-gel proteome of seedlings exposed to mild cadmium stress; 21 proteins were upregulated. Reason: Only the abstract is cached, and it does not name lipoamide dehydrogenase among the induced proteins or say how the spot was assigned to mtLPD1 rather than its 94%-identical paralog mtLPD2. We cannot see the data behind the annotation. If confirmed, it would be a stress-responsive abundance change and non-core. Supporting Evidence: PMID:20005002 Of the 730 reproducible proteins among all gels, 21 were statistically upregulated in response to Cd.
GO:0048046 apoplast	HDA PMID:18538804 Hydroponic isotope labelling of entire plants (HILEP) for qu...	MARK AS OVER ANNOTATED	Summary: Detected in a quantitative proteomics study of apoplastic and whole-plant protein extracts under oxidative stress. Reason: mtLPD1 has an experimentally verified mitochondrial transit peptide and no secretion signal, and acts in the matrix. A single high-throughput hit in an apoplast fraction most likely reflects carry-over of an abundant leaf mitochondrial protein. Following projects/ARATH/organelle-audit.md, such an HDA hit for a protein localized elsewhere is marked as over-annotated rather than removed. Supporting Evidence: PMID:18538804 it was possible to show differential protein expression in the apoplast of plants submitted to oxidative stress file:ARATH/mtLPD1/mtLPD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0050660 flavin adenine dinucleotide binding	IBA GO_REF:0000033	ACCEPT	Summary: FAD binding, the prosthetic group of the E3 flavoprotein. Reason: FAD is the obligatory redox cofactor of lipoamide dehydrogenase, and the FAD-binding residues are conserved in mtLPD1. Same action as the mtLPD2 review. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt Note=Binds 1 FAD per subunit. PMID:22303256 Electrons are first transferred to the co-factor FAD that is re-oxidized by NAD + resulting in the formation of NADH
GO:0050660 flavin adenine dinucleotide binding	IEA GO_REF:0000002	ACCEPT	Summary: FAD binding inferred from the lipoamide dehydrogenase InterPro signature. Reason: Consistent with the IBA row and the conserved FAD-binding residues. Supporting Evidence: file:ARATH/mtLPD1/mtLPD1-uniprot.txt Note=Binds 1 FAD per subunit.
GO:0050897 cobalt ion binding	HDA PMID:20018591 Divalent metal ions in plant mitochondria and their role in ...	MARK AS OVER ANNOTATED	Summary: Retained on Co2+-charged IMAC of mitochondrial proteins. Reason: IMAC retention does not establish physiological cobalt binding. Cobalt is present in mitochondria only in trace amounts, and LPD has no known cobalt site. Same action as the mtLPD2 review. Supporting Evidence: PMID:20018591 revealing a 26:8:6:1 molar ratio for iron:zinc:copper:manganese and trace amounts of cobalt and molybdenum
GO:0005960 glycine cleavage complex	IDA PMID:32311173 Stoichiometry of two plant glycine decarboxylase complexes a...	NEW	Summary: Mass-spectrometric stoichiometry of the Arabidopsis leaf glycine decarboxylase complex detects both L-protein isoforms, with about four times more GCS-L1 (mtLPD1) than GCS-L2 (mtLPD2). Reason: GOA has no glycine cleavage complex annotation for mtLPD1, although the L protein is one of the four defining components of the P/H/T/L complex and mtLPD1 is the main L isoform of the leaf complex. The sibling reviews GLDP1 and GLDP2 add the same term from the same paper. L proteins in other species carry the term (pea mitochondrial LPD P31023 by IDA, yeast LPD1 P09624 by IMP in QuickGO), so no convention excludes the shared E3. Caveat - the cached abstract does not give loci; GCS-L1 is mapped to At1g48030 using the same group's nomenclature, GDC-L1 = mtLPD1 = At1g48030. Supporting Evidence: PMID:32311173 The Arabidopsis GDC contains four times more of the isoforms GCS-P1 and GCS-L1 in comparison with GCS-P2 and GCS-L2 PMID:31413204 GDC-L1 (mtLPD1; At1g48030), GDC-L2 (AT3G17240) file:ARATH/mtLPD1/mtLPD1-uniprot.txt Part of both the glycine cleavage system composed of four proteins: P, T, L and H
GO:0019464 glycine decarboxylation via glycine cleavage system	TAS PMID:22303256 Photorespiration.	NEW	Summary: As the GDC L protein, mtLPD1 catalyses the last step of the glycine cleavage cycle, the NAD+-dependent reoxidation of the reduced lipoyl arm of the H protein. Reason: Participation test - the L protein catalyses one of the three enzymatic steps of the glycine cleavage system and so does part of the work of the process. It is not merely required for it. Comparator check (QuickGO) - pea mitochondrial LPD P31023 carries GO:0019464 by IDA and yeast LPD1 by RCA, and the sibling GDC subunit reviews (GLDP1, GLDP2, GDCST, GDCH) accept the term. GOA has no glycine cleavage process annotation for either Arabidopsis mitochondrial LPD. mtLPD1-specific support comes from its predominance in the leaf GDC (PMID:32311173) and its predominant role in photorespiration in mutants (PMID:41990722). The term is not an ancestor or descendant of GO:0009853 photorespiration, which is proposed separately. Supporting Evidence: PMID:22303256 This reaction is catalyzed by L-protein, a homodimeric dihydrolipoamide dehydrogenase (EC 1.8.1.4). PMID:22303256 two genes each for P-protein (At4g33010 and At2g26080) and L-protein (At3g17240 and At1g48030) PMID:32311173 The Arabidopsis GDC contains four times more of the isoforms GCS-P1 and GCS-L1 in comparison with GCS-P2 and GCS-L2
GO:0009853 photorespiration	IMP PMID:41990722 Crucial roles of the mitochondrial lipoamide dehydrogenase i...	NEW	Summary: Loss-of-function mutant analysis of the two Arabidopsis mtLPDs shows that both contribute to photorespiration and that mtLPD1 has the predominant role, especially under high light. Reason: Participation test - mtLPD1 catalyses a step of the photorespiratory C2 cycle (reoxidation of the H-protein lipoyl arm in mitochondrial glycine decarboxylation), so it does part of the work of the process. It is not merely required for it. Comparator check (QuickGO, Arabidopsis, GO:0009853) - enzymes for other C2-cycle steps carry the term (SHM1, GLYK, HPR, GGAT1, PLGG1), whereas no GDC subunit does in GOA. The sibling reviews GLDP1, GLDP2, GDCST and GDCH each add this term as NEW. Unlike mtLPD2, for which no NEW photorespiration row was proposed, mtLPD1 has gene-specific evidence - mutant analysis showing it is the predominant isoform for photorespiration, the 4-fold excess of L1 over L2 in the leaf GDC, and strong leaf and light-induced expression. The mutant paper is abstract-only, so allele details and assays could not be checked; the claim is stated directly in the abstract. Not an ancestor or descendant of GO:0019464. Supporting Evidence: PMID:41990722 While the two mtLPDs both contribute to photorespiration, mtLPD1 plays a more predominant role, especially under high-light stress. PMID:38861078 in illuminated, photosynthesizing tissue a vast amount of mtLPD1 is necessary for glycine decarboxylase (GDC), the key enzyme of photorespiration PMID:32311173 The Arabidopsis GDC contains four times more of the isoforms GCS-P1 and GCS-L1 in comparison with GCS-P2 and GCS-L2

Gene Description

Existing Annotations Review

Core Functions

L protein of the mitochondrial glycine decarboxylase complex. This FAD flavoprotein reoxidizes the dihydrolipoyl arm of the H protein with NAD+, producing NADH and completing each glycine cleavage cycle. mtLPD1 is the main L isoform of the leaf complex and the predominant mtLPD in photorespiration.

Shared E3 of the mitochondrial 2-oxoacid dehydrogenase complexes, including the 2-oxoglutarate dehydrogenase complex of the TCA cycle. In this role mtLPD1 overlaps with its paralog mtLPD2.

References

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