ALD5

UniProt ID: P40047
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

Ald5p is a minor mitochondrial aldehyde dehydrogenase of S. cerevisiae, targeted to the matrix by a 23-residue N-terminal presequence. The recombinant enzyme oxidizes acetaldehyde and propanal using NAD+ or NADP+ without strong cofactor preference and is strongly stimulated by K+, but it has much lower catalytic efficiency than Ald4p or Ald6p. Genetic studies show that Ald5p provides the mitochondrial contribution to acetate formation during anaerobic growth on glucose, second to the cytosolic Ald6p. ald5 mutants also show reduced respiration and cytochrome content, suggesting an additional, poorly understood role in maintaining the mitochondrial electron transport chain. Ald5p makes at most a minor contribution to acetaldehyde oxidation during growth on ethanol.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004029 aldehyde dehydrogenase (NAD+) activity
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA aldehyde dehydrogenase (NAD+) activity from the class-1/2 ALDH node PTN000192666 (ALD5 itself, SGD:S000000875, is among the donors).
Reason: Recombinant Ald5p uses NAD+ as well as NADP+ (K+ stimulates NAD-linked activity 40-fold), so the inherited NAD+-ALDH activity holds for the target, although its NAD-linked turnover is low.
Supporting Evidence:
PMID:9473035
Mitochondrial ALDH5 could use either NAD or NADP as the cofactor and did not show a preference.
PMID:9473035
In contrast, the activity of ALDH5 increased in the presence of K + ions: 15-fold with NADP and 40-fold with NAD, respectively.
GO:0004029 aldehyde dehydrogenase (NAD+) activity
IDA
PMID:9473035
Molecular cloning, characterization, and potential roles of ... 		ACCEPT
Summary: IDA from Wang et al. 1998 (recombinant ALDH5 = Ald5p) assayed with NAD+.
Reason: Wang et al. purified recombinant Ald5p and showed NAD+- and NADP+-dependent aldehyde oxidation; correct, though Ald5p is kinetically a poor enzyme.
Supporting Evidence:
PMID:9473035
Mitochondrial ALDH5 could use either NAD or NADP as the cofactor and did not show a preference.
PMID:9473035
Our in vitro enzyme kinetic data (Tables 3 and 4 ) suggest that ALDH5 is a relatively poor enzyme compared to the other two.
GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity
IDA
PMID:9473035
Molecular cloning, characterization, and potential roles of ... 		ACCEPT
Summary: IDA aldehyde dehydrogenase [NAD(P)+] activity from Wang et al. 1998.
Reason: Ald5p uses NAD+ or NADP+ without strong preference; this grouping term best describes its activity and is used as the core MF.
Supporting Evidence:
PMID:9473035
Mitochondrial ALDH5 could use either NAD or NADP as the cofactor and did not show a preference.
GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity
RCA
GO_REF:0000123 		ACCEPT
Summary: RCA from YeastPathways superpathway of glucose fermentation (acetaldehyde + NAD(P)+ -> acetate).
Reason: Supported for Ald5p: Saint-Prix et al. showed ald5 deletion reduces acetate formation during anaerobic growth on glucose. MF correct.
Supporting Evidence:
PMID:15256563
The deletion of ALD6 and ALD5 decreased acetate formation in both strains, demonstrating for the first time that the mitochondrial Ald5p isoform is involved in the biosynthesis of acetate during anaerobic growth on glucose.
GO:0005739 mitochondrion
HDA
PMID:14576278
The proteome of Saccharomyces cerevisiae mitochondria. 		ACCEPT
Summary: HDA mitochondrion from Sickmann et al. 2003 mitochondrial proteome.
Reason: Consistent with Ald5p's N-terminal presequence and in vitro mitochondrial import.
Supporting Evidence:
PMID:14576278
The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS.
file:yeast/ALD5/ALD5-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005739 mitochondrion
HDA
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen... 		ACCEPT
Summary: HDA mitochondrion from Reinders et al. 2006.
Reason: Consistent with established mitochondrial location.
Supporting Evidence:
PMID:16823961
Proteomic analyses of different subcellular compartments, so-called organellar proteomics
GO:0005739 mitochondrion
HDA
PMID:24769239
Quantitative variations of the mitochondrial proteome and ph... 		ACCEPT
Summary: HDA mitochondrion from Renvoise et al. 2014.
Reason: Consistent with established mitochondrial location.
Supporting Evidence:
PMID:24769239
Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA is_active_in mitochondrion from PTN000916385 (yeast ALD4/ALD5/ALD6 seeds).
Reason: Correct for Ald5p, a presequence-containing mitochondrial ALDH.
Supporting Evidence:
PMID:9473035
The experiments with ALDH5-LacZ fusion protein and in vitro import into isolated mitochondria confirmed that ALDH5 was located in mitochondria (data not shown).
GO:0005739 mitochondrion
IDA
PMID:10585550
Involvement of mitochondrial aldehyde dehydrogenase ALD5 in ... 		ACCEPT
Summary: IDA mitochondrion from Kurita and Nishida 1999, which measured K+-activated ALDH activity in mitochondrial fractions of ald5 mutants.
Reason: The abstract reports reduced mitochondrial-fraction K+-ALDH activity in the ald5 mutant; together with Wang et al.'s import data this supports mitochondrial location.
Supporting Evidence:
PMID:10585550
K(+)-activated ALDH activity of the ald5 mutant was about 80% of the wild-type in the mitochondrial fraction, while the respiratory activity of the ald5 mutant was greatly reduced.
GO:0005759 mitochondrial matrix
EXP
PMID:9473035
Molecular cloning, characterization, and potential roles of ... 		ACCEPT
Summary: EXP mitochondrial matrix from Wang et al. 1998 (ALDH5-LacZ fusion and in vitro import into mitochondria).
Reason: Import of the presequence fusion into isolated mitochondria indicates matrix targeting; UniProt records matrix location. Core location.
Supporting Evidence:
PMID:9473035
The experiments with ALDH5-LacZ fusion protein and in vitro import into isolated mitochondria confirmed that ALDH5 was located in mitochondria (data not shown).
PMID:9473035
we deduce that the first 23 amino acids code for a putative mitochondrial leader sequence
file:yeast/ALD5/ALD5-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix
IEA
GO_REF:0000120 		ACCEPT
Summary: IEA mitochondrial matrix (ARBA / UniProt SubCell SL-0170).
Reason: Correct, matches experimental evidence.
Supporting Evidence:
file:yeast/ALD5/ALD5-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005829 cytosol
RCA
GO_REF:0000123 		REMOVE
Summary: RCA is_active_in cytosol from YeastPathways superpathway of glucose fermentation.
Reason: Compartment inherited from the cytosolic PDH-bypass reaction in the pathway model. Ald5p is a mitochondrial matrix enzyme with a cleavable presequence; Saint-Prix et al. explicitly describe its contribution to acetate as a mitochondrial route. Contradicted by experimental localization.
Supporting Evidence:
PMID:9473035
The experiments with ALDH5-LacZ fusion protein and in vitro import into isolated mitochondria confirmed that ALDH5 was located in mitochondria (data not shown).
PMID:15256563
Thus, acetate is mainly produced by the cytosolic PDH bypass via Ald6p and by a mitochondrial route involving Ald5p.
GO:0006068 ethanol catabolic process
IEA
GO_REF:0000041 		KEEP AS NON CORE
Summary: IEA ethanol catabolic process from UniPathway UPA00780 (ethanol degradation, acetate from ethanol step 2).
Reason: Ald5p can oxidize acetaldehyde, and ald5 disruption slowed growth on ethanol in Wang et al., but the same authors conclude its role in acetaldehyde metabolism appears unimportant and its kinetics are poor; Ald4p and Ald6p dominate ethanol oxidation. Minor contribution only.
Supporting Evidence:
PMID:9473035
The growth of strains with single ALD1 (HWT6) and ALD5 (HWL18) disruptions on ethanol was slower than that of TWY397, with the slowest growth found with HWL18.
PMID:9473035
The role of mitochondrial ALDH5 in acetaldehyde metabolism has not been defined but appears to be unimportant.
GO:0016491 oxidoreductase activity
IEA
GO_REF:0000002 		TOO GENERAL
Summary: InterPro2GO IEA generic oxidoreductase activity.
Reason: Correct but uninformative; specific ALDH terms are present.
GO:0019413 acetate biosynthetic process
IEA
GO_REF:0000117 		ACCEPT
Summary: ARBA IEA acetate biosynthetic process.
Reason: Consistent with the experimental evidence that Ald5p contributes to acetate formation during fermentation.
Supporting Evidence:
PMID:15256563
The deletion of ALD6 and ALD5 decreased acetate formation in both strains, demonstrating for the first time that the mitochondrial Ald5p isoform is involved in the biosynthesis of acetate during anaerobic growth on glucose.
GO:0019413 acetate biosynthetic process
IMP
PMID:15256563
Functional analysis of the ALD gene family of Saccharomyces ... 		ACCEPT
Summary: IMP acetate biosynthetic process from Saint-Prix et al. 2004.
Reason: ald5 deletion decreased acetate formation in two strain backgrounds during anaerobic growth on glucose; Ald5p is the mitochondrial contributor to acetate after Ald6p. Core process.
Supporting Evidence:
PMID:15256563
The deletion of ALD6 and ALD5 decreased acetate formation in both strains, demonstrating for the first time that the mitochondrial Ald5p isoform is involved in the biosynthesis of acetate during anaerobic growth on glucose.
PMID:15256563
Thus, acetate is mainly produced by the cytosolic PDH bypass via Ald6p and by a mitochondrial route involving Ald5p.
GO:0019658 bifid shunt
RCA
GO_REF:0000123 		REMOVE
Summary: RCA bifid shunt from YeastPathways superpathway of glucose fermentation.
Reason: The bifid shunt is the bifidobacterial phosphoketolase pathway, absent from S. cerevisiae; the term is an artefact of the superpathway mapping.
GO:0033721 aldehyde dehydrogenase (NADP+) activity
EXP
PMID:9473035
Molecular cloning, characterization, and potential roles of ... 		ACCEPT
Summary: EXP aldehyde dehydrogenase (NADP+) activity from Wang et al. 1998.
Reason: Recombinant Ald5p oxidizes aldehydes with NADP+; correct.
Supporting Evidence:
PMID:9473035
Mitochondrial ALDH5 could use either NAD or NADP as the cofactor and did not show a preference.
file:yeast/ALD5/ALD5-uniprot.txt
Reaction=an aldehyde + NADP(+) + H2O = a carboxylate + NADPH + 2 H(+);
GO:0033721 aldehyde dehydrogenase (NADP+) activity
IEA
GO_REF:0000120 		ACCEPT
Summary: IEA from EC 1.2.1.4 / Rhea (RHEA:11888, RHEA:27918).
Reason: Matches experimentally recorded activity; correct.
Supporting Evidence:
file:yeast/ALD5/ALD5-uniprot.txt
Reaction=an aldehyde + NADP(+) + H2O = a carboxylate + NADPH + 2 H(+);
GO:0033721 aldehyde dehydrogenase (NADP+) activity
RCA
GO_REF:0000123 		ACCEPT
Summary: RCA from YeastPathways superpathway of glucose fermentation (EC 1.2.1.4).
Reason: MF correct for Ald5p.
Supporting Evidence:
file:yeast/ALD5/ALD5-uniprot.txt
Reaction=an aldehyde + NADP(+) + H2O = a carboxylate + NADPH + 2 H(+);
GO:0140088 acetaldehyde dehydrogenase (NADP+) activity
EXP
PMID:9473035
Molecular cloning, characterization, and potential roles of ... 		ACCEPT
Summary: EXP acetaldehyde dehydrogenase (NADP+) activity from Wang et al. 1998.
Reason: UniProt records acetaldehyde + NADP+ -> acetate for Ald5p with kinetic data from this paper (Km acetaldehyde 0.058 mM, Vmax 1.1 umol/min/mg). Specific physiological activity behind its acetate-forming role.
Supporting Evidence:
file:yeast/ALD5/ALD5-uniprot.txt
Reaction=acetaldehyde + NADP(+) + H2O = acetate + NADPH + 2 H(+);
GO:0140088 acetaldehyde dehydrogenase (NADP+) activity
IEA
GO_REF:0000120 		ACCEPT
Summary: IEA (ARBA / RHEA:25298) acetaldehyde dehydrogenase (NADP+) activity.
Reason: Correct, matches experimental activity.
Supporting Evidence:
file:yeast/ALD5/ALD5-uniprot.txt
Reaction=acetaldehyde + NADP(+) + H2O = acetate + NADPH + 2 H(+);

Core Functions

Minor mitochondrial matrix K+-activated aldehyde dehydrogenase that oxidizes acetaldehyde to acetate with NAD+ or NADP+, providing the mitochondrial contribution to acetate formation during anaerobic glucose fermentation.

Molecular Function:
aldehyde dehydrogenase [NAD(P)+] activity
Directly Involved In:
acetate biosynthetic process
Cellular Locations:
mitochondrial matrix
Supporting Evidence:
  • PMID:9473035
    Mitochondrial ALDH5 could use either NAD or NADP as the cofactor and did not show a preference.
  • PMID:15256563
    The deletion of ALD6 and ALD5 decreased acetate formation in both strains, demonstrating for the first time that the mitochondrial Ald5p isoform is involved in the biosynthesis of acetate during anaerobic growth on glucose.
  • PMID:15256563
    Thus, acetate is mainly produced by the cytosolic PDH bypass via Ald6p and by a mitochondrial route involving Ald5p.
  • PMID:9473035
    The experiments with ALDH5-LacZ fusion protein and in vitro import into isolated mitochondria confirmed that ALDH5 was located in mitochondria (data not shown).
  • file:yeast/ALD5/ALD5-uniprot.txt
    Reaction=acetaldehyde + NADP(+) + H2O = acetate + NADPH + 2 H(+);

References

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Suggested Questions for Experts

Q: Is the respiratory/cytochrome deficiency of ald5 mutants caused by loss of Ald5p catalytic activity (e.g. on a specific aldehyde) or by a non-catalytic role?

Q: Does Ald5p have a preferred physiological substrate other than acetaldehyde, given its poor kinetics with acetaldehyde?

Suggested Experiments

Experiment: Complement ald5 with a catalytic-cysteine mutant of Ald5p and assay respiration, cytochrome content and acetate production to separate catalytic from non-catalytic roles.

Deep Research

SGD

(ALD5-deep-research-sgd.md)
SGD gene description for ALD5 (yeast) SGD

SGD gene description for ALD5 (yeast)

Mitochondrial aldehyde dehydrogenase; involved in regulation or biosynthesis of electron transport chain components and acetate formation; activated by K+; utilizes NADP+ as the preferred coenzyme; constitutively expressed

📚 Additional Documentation

Notes

(ALD5-notes.md)

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