The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The literature gathered here is consistent with the UniProt target P54216 being C. elegans fructose-bisphosphate aldolase 1 (FBA1): a comparative aldolase phylogeny explicitly lists “Caenorhabditis elegans FBA 1 (P54216).” (pirovich2021multifunctionalfructose16bisphosphate pages 3-5)
Independent C. elegans transcriptomics evidence maps the gene symbol aldo-1 to the genomic ORF T05D4.1, annotated as “fructose bisphosphate aldolase.” (miersch2012sexdifferencesin pages 13-15)
Accordingly, this report focuses on the C. elegans glycolytic aldolase encoded by aldo-1/T05D4.1 and linked to UniProt P54216, and does not mix in “aldo-1” usages from other organisms. (pirovich2021multifunctionalfructose16bisphosphate pages 3-5, miersch2012sexdifferencesin pages 13-15)
Fructose-1,6-bisphosphate aldolase is a core glycolytic enzyme that catalyzes the cleavage of the substrate fructose-1,6-bisphosphate (F1,6BP) in glycolysis (classically the “fourth step” of glycolysis in many pathway descriptions). (pirovich2021multifunctionalfructose16bisphosphate pages 3-5)
In C. elegans, aldo-1 (T05D4.1) is annotated as “fructose bisphosphate aldolase” and is placed in glucose metabolism in a curated gene list; the table’s reaction description explicitly notes the substrate fructose-1,6-bisphosphate and the glycolytic product glyceraldehyde-3-phosphate (as written in the source table). (miersch2012sexdifferencesin pages 13-15)
Fructose-bisphosphate aldolases are subdivided into mechanistic/structural classes. In nematode aldolases, a class-I-type mechanism involves a conserved lysine that forms a Schiff-base intermediate with the substrate. In a nematode aldolase structural/biochemical analysis that includes C. elegans aldo-1 as a homolog in the sequence alignment, the authors highlight that “the lysine at position 230 is the residue where Schiff base intermediates are formed,” consistent with the canonical class I aldolase catalytic strategy. (umair2021teladorsagiacircumcincta16bisphosphate pages 4-8)
The primary function of C. elegans ALDO-1 is its glycolytic aldolase activity on F1,6BP within glucose metabolism. (miersch2012sexdifferencesin pages 13-15, pujol2013succinatedehydrogenaseupregulation pages 2-4)
Although the retrieved corpus did not include a direct biochemical purification/kinetic paper for C. elegans ALDO-1 itself, nematode aldolase kinetic measurements in a closely related context report clear activity on fructose 1,6-bisphosphate with an apparent Km = 0.24 ± 0.01 µM and Vmax = 432 nmol·min⁻¹·mg⁻¹ at 30°C, with optimum pH 7.5 (n=3). These parameters support strong specificity/efficiency for F1,6BP in nematode class-I-type aldolases and are consistent with the conserved role inferred for C. elegans ALDO-1 based on homology and pathway placement. (umair2021teladorsagiacircumcincta16bisphosphate pages 4-8)
A comparative aldolase phylogeny built from UniProt sequences includes C. elegans FBA1 (P54216) among other eukaryotic aldolases, supporting placement of P54216 within conserved fructose-bisphosphate aldolase families. (pirovich2021multifunctionalfructose16bisphosphate pages 3-5)
In a study on sex differences in carbohydrate metabolism, aldo-1 (T05D4.1) shows higher expression in males than hermaphrodites. The male:hermaphrodite expression ratios for two transcript entries are approximately 2.11–2.12 in young adults and 2.33–2.85 in adults (significance denoted by asterisks in the table). (miersch2012sexdifferencesin pages 13-15)
A neuron-focused aging transcriptomics study reports that canonical metabolic genes, including glycolytic enzymes, decline in aging male neurons. In that context, aldo-1 is listed among glycolysis enzymes that are “downregulated with age at least 2-fold” (Figure 5B) in male neurons, within a DESeq2 framework using thresholds including adjusted p-values (p-adj) < 0.05 for differential expression calls. (weng2024malespecificbehavioraland pages 7-9)
No retrieved C. elegans primary study snippet in this run provided direct experimental subcellular localization for ALDO-1 (e.g., cytosolic vs organelle-associated). Thus, localization cannot be asserted beyond the strong family-level expectation that aldolase participates in cytosolic glycolysis; broader aldolase reviews discuss intracellular (and sometimes extracellular “moonlighting”) localizations across organisms, but this is not direct C. elegans ALDO-1 localization evidence. (pirovich2021multifunctionalfructose16bisphosphate pages 3-5)
In C. elegans mitochondrial complex I mutants, aldo-1 is transcriptionally upregulated, consistent with a metabolic shift toward glycolysis:
- gas-1(fc21): ~3-fold aldo-1 increase
- nuo-6(qm200): ~6-fold aldo-1 increase (pujol2013succinatedehydrogenaseupregulation pages 2-4)
Functional evidence links aldo-1 to survival/longevity in these mitochondrial mutants. RNAi knockdown of aldo-1:
- decreased gas-1(fc21) median lifespan by up to 65%
- decreased nuo-6(qm200) median lifespan by >85% (pujol2013succinatedehydrogenaseupregulation pages 2-4)
The authors interpret these results as indicating that these mutants “rely heavily on glycolysis for energy production,” positioning ALDO-1 as a critical component of compensatory energy metabolism when oxidative phosphorylation is impaired. (pujol2013succinatedehydrogenaseupregulation pages 2-4)
In a 2024 transcriptome analysis of mutants with persistent HIF-1 over-activation (loss of negative regulators including vhl-1, egl-9, rhy-1), aldo-1 is among the genes “commonly up-regulated” in all three mutants and is explicitly annotated as “aldo-1 (fructose-1,6-bisphosphate aldolase).” (feng2024transcriptomeanalysesdescribe pages 4-5)
The gene set shared across mutants (104 upregulated genes) shows strong statistical overlap (reported p-values < 2.2E-16 by Fisher’s exact tests), and the shared upregulated set is enriched for “Metabolism” at WormCat Category 1 (Bonferroni FDR = 9.23E-07), with aldo-1 listed within that metabolism-enriched gene list. (feng2024transcriptomeanalysesdescribe pages 4-5)
This provides recent evidence that aldo-1 is part of a HIF-linked metabolic transcriptional program relevant to hypoxia adaptation in C. elegans. (feng2024transcriptomeanalysesdescribe pages 4-5)
Two 2024 studies in the retrieved corpus provide modern systems-level contexts for aldo-1 regulation:
1) Neuron aging: male neuron transcriptomes show ≥2-fold age-associated downregulation of glycolysis genes including aldo-1 (with DESeq2 and p-adj reporting in the analysis pipeline). (weng2024malespecificbehavioraland pages 7-9)
2) Persistent HIF-1 activation: aldo-1 is part of a shared upregulated gene set in HIF-1 high-activity mutants; the overlap across mutants is highly significant (p < 2.2E-16), and metabolism enrichment is supported (Bonferroni FDR 9.23E-07). (feng2024transcriptomeanalysesdescribe pages 4-5)
Within the retrieved literature, aldo-1 functions as a high-value metabolic readout and dependency in contexts where glycolytic flux is predicted to change:
- As a marker/effector of compensatory glycolysis in mitochondrial respiratory chain mutants (with strong functional impact of knockdown on lifespan). (pujol2013succinatedehydrogenaseupregulation pages 2-4)
- As part of transcriptional programs in hypoxia/HIF-1 biology. (feng2024transcriptomeanalysesdescribe pages 4-5)
- As part of metabolic decline signatures in neuron aging. (weng2024malespecificbehavioraland pages 7-9)
A 2021 review emphasizes that fructose-1,6-bisphosphate aldolase is not only a conserved glycolytic enzyme but can have “moonlighting” functions and can be targeted by drugs or vaccines in pathogenic contexts (broadly across organisms). While this is not an implementation of C. elegans ALDO-1 specifically, it contextualizes why aldolase family members are studied as potential targets and why conserved sequence/function matter. (pirovich2021multifunctionalfructose16bisphosphate pages 3-5)
The strongest C. elegans-specific functional evidence available in this run indicates that aldo-1 is essential for adaptive glycolysis in settings where mitochondrial respiration is compromised (complex I mutants), with large median-lifespan penalties upon aldo-1 knockdown (up to 65% and >85%). (pujol2013succinatedehydrogenaseupregulation pages 2-4)
Recent (2024) systems-level studies position aldo-1 at the intersection of hypoxia signaling (HIF-1) and sex/age-dependent neuronal metabolic decline, suggesting that glycolysis regulation (including aldolase) is a recurrent node in how C. elegans adjusts energy metabolism across stress and aging contexts. (feng2024transcriptomeanalysesdescribe pages 4-5, weng2024malespecificbehavioraland pages 7-9)
At the molecular level, class-I-type aldolase Schiff-base chemistry is supported by conserved mechanistic residues in nematode homologs and is consistent with the protein family assignment for P54216, but this remains inference rather than a direct mechanistic experiment on the C. elegans protein in the retrieved texts. (umair2021teladorsagiacircumcincta16bisphosphate pages 4-8, pirovich2021multifunctionalfructose16bisphosphate pages 3-5)
| Topic | Key finding | Quantitative details (fold change, FDR/p-adj, lifespan %) | System/condition (strain/tissue) | Source (authors, year, journal) | Publication date (month/year) | URL/DOI | Evidence strength/notes |
|---|---|---|---|---|---|---|---|
| Identity | UniProt P54216 is listed as Caenorhabditis elegans FBA 1, supporting assignment of the target protein to C. elegans fructose-bisphosphate aldolase 1. | None reported in snippet. | Comparative aldolase phylogeny; C. elegans sequence entry. | Pirovich et al., 2021, Frontiers in Molecular Biosciences | Aug 2021 | https://doi.org/10.3389/fmolb.2021.719678 | Useful accession-level confirmation for P54216; review/phylogeny rather than direct worm functional experiment. (pirovich2021multifunctionalfructose16bisphosphate pages 3-5) |
| Identity | ORF T05D4.1 is explicitly annotated as aldo-1, “fructose bisphosphate aldolase,” confirming aldo-1 ↔ T05D4.1 mapping in C. elegans. | Male:hermaphrodite ratios shown for two transcript entries: T05D4.1.2 = 2.11 (young adult), 2.85 (adult); T05D4.1.1 = 2.12 (young adult), *2.33 (adult). | Whole-animal sex-comparison transcriptomics in young adult and adult worms. | Miersch & Döring, 2012, PLoS ONE | Sep 2012 | https://doi.org/10.1371/journal.pone.0044748 | Strong direct mapping for the gene name/ORF in C. elegans; asterisks indicate significance but exact p-value thresholds were not present in snippet. (miersch2012sexdifferencesin pages 13-15) |
| Function | aldo-1 is a glycolytic fructose-bisphosphate aldolase catalyzing cleavage of fructose-1,6-bisphosphate toward glyceraldehyde-3-phosphate (table wording shows reaction direction). | Reaction shown as “fructose-1,6 bisphosphate → glyceraldehyd-3 phosphate” in the table; aldolase is also described as catalyzing the fourth step of glycolysis. | C. elegans carbohydrate metabolism annotation; general aldolase biochemistry review. | Miersch & Döring, 2012, PLoS ONE; Pirovich et al., 2021, Frontiers in Molecular Biosciences | Sep 2012; Aug 2021 | https://doi.org/10.1371/journal.pone.0044748 ; https://doi.org/10.3389/fmolb.2021.719678 | Strong for pathway-level enzymatic role; the full stoichiometric coproduct list is not fully printed in the Miersch table snippet, but aldolase substrate context is explicit. (miersch2012sexdifferencesin pages 13-15, pirovich2021multifunctionalfructose16bisphosphate pages 3-5) |
| Function / mechanism | Aldolases of this family use a class I Schiff-base mechanism; conserved active-site residues are retained in nematode homologs including C. elegans aldo-1 in sequence alignment context. | In homologous enzyme model, Lys230 is the Schiff-base residue; kinetic values for recombinant nematode aldolase: Km = 0.24 ± 0.01 µM, Vmax = 432 nmol min−1 mg−1, optimum pH 7.5, n = 3. | Comparative nematode aldolase biochemistry/structure (Teladorsagia with C. elegans aldo-1 in alignment). | Umair et al., 2021, Parasitologia | Jan 2021 | https://doi.org/10.3390/parasitologia1010001 | Indirect but informative for ALDO-1 because the study includes C. elegans aldo-1 among homologs and highlights conserved catalytic residues typical of class I aldolases. (umair2021teladorsagiacircumcincta16bisphosphate pages 4-8) |
| Expression-regulation | aldo-1 expression is higher in males than in hermaphrodites, consistent with sex-biased carbohydrate metabolism. | Male:hermaphrodite expression ratios: 2.11 and 2.12 in young adults; 2.85 and *2.33 in adults for two T05D4.1 transcript entries. | Whole animals; young adult and adult stages. | Miersch & Döring, 2012, PLoS ONE | Sep 2012 | https://doi.org/10.1371/journal.pone.0044748 | Direct C. elegans evidence; no tissue localization given in snippet. (miersch2012sexdifferencesin pages 13-15) |
| Pathway / phenotype | In mitochondrial complex I mutants, aldo-1 is strongly upregulated, supporting increased glycolytic dependence. | ~3-fold increase in gas-1(fc21); ~6-fold increase in nuo-6(qm200). | Day-1 adults from synchronized populations; qRT-PCR in mitochondrial mutant worms. | Pujol et al., 2013, PLoS ONE | Mar 2013 | https://doi.org/10.1371/journal.pone.0059493 | Strong direct evidence connecting aldo-1 to metabolic rewiring in vivo. (pujol2013succinatedehydrogenaseupregulation pages 2-4) |
| Phenotype | aldo-1 is functionally important for survival/longevity of complex I mutants; RNAi knockdown greatly shortens lifespan. | In gas-1(fc21), median lifespan decreased by up to 65% after aldo-1 RNAi; in nuo-6(qm200), aldo-1 downregulation decreased median lifespan by >85%. | RNAi in mitochondrial complex I mutant worms. | Pujol et al., 2013, PLoS ONE | Mar 2013 | https://doi.org/10.1371/journal.pone.0059493 | Strong phenotype-to-function link; indicates reliance on glycolysis when respiration is impaired. (pujol2013succinatedehydrogenaseupregulation pages 2-4) |
| Pathway | Authors conclude both complex I mutants “rely heavily on glycolysis for energy production,” placing aldo-1 in compensatory metabolic adaptation. | Lifespan sensitivity to aldo-1 RNAi as above; icl-1 had milder effects by comparison. | gas-1(fc21) and nuo-6(qm200) mitochondrial dysfunction models. | Pujol et al., 2013, PLoS ONE | Mar 2013 | https://doi.org/10.1371/journal.pone.0059493 | Strong pathway inference because supported by expression plus functional RNAi data. (pujol2013succinatedehydrogenaseupregulation pages 2-4) |
| Recent studies | Persistent HIF-1 over-activation upregulates aldo-1 as part of a shared metabolic response in three HIF-1 high-activity mutants. | aldo-1 is in the 104 genes upregulated in all three mutants; enriched WormCat Cat1: Metabolism, 23 genes, Bonferroni FDR = 9.23E-07; overlaps significant at p < 2.2E-16. | C. elegans vhl-1(ok161), egl-9(sa307), rhy-1(ok1402) mutants. | Feng et al., 2024, PLOS ONE | Mar 2024 | https://doi.org/10.1371/journal.pone.0295093 | Strong recent evidence for transcriptional regulation in hypoxia/HIF biology; no gene-specific fold change for aldo-1 in snippet. (feng2024transcriptomeanalysesdescribe pages 4-5) |
| Recent studies / tissue context | In aging male neurons, aldo-1 is among glycolytic genes that decline with age, linking it to neuronal energetic aging. | Downregulated with age by at least 2-fold; significance framework in study used DESeq2, cutoff log2 fold-change > 0.5 or < -0.5, p-adj < 0.05. | Sorted male neurons during aging; compared young vs aged neuronal transcriptomes. | Weng & Murphy, 2024, iScience | Jun 2024 | https://doi.org/10.1016/j.isci.2024.109910 | Strong recent tissue-specific transcriptomic evidence; snippet does not provide aldo-1-specific adjusted p-value. (weng2024malespecificbehavioraland pages 7-9, weng2024malespecificbehavioraland pages 9-12) |
| Expression/localization | Direct subcellular localization of C. elegans ALDO-1 was not provided in the retrieved worm-specific snippets; canonical aldolase literature describes aldolase as a cytosolic glycolytic enzyme, with moonlighting/extracellular roles in other systems. | None for C. elegans ALDO-1 in snippets. | General aldolase biology review; not worm-specific localization experiment. | Pirovich et al., 2021, Frontiers in Molecular Biosciences | Aug 2021 | https://doi.org/10.3389/fmolb.2021.719678 | Caution: relevant for family-level inference, not direct localization evidence for C. elegans aldo-1. (pirovich2021multifunctionalfructose16bisphosphate pages 3-5) |
| Applications | Aldolase is highlighted broadly as a therapeutic target, with inhibitor and vaccine interest in pathogens; this supports translational relevance of conserved aldolase biology, though not a direct C. elegans application. | No C. elegans-specific implementation metrics in snippet. | Cross-species/pathogen aldolase biology. | Pirovich et al., 2021, Frontiers in Molecular Biosciences | Aug 2021 | https://doi.org/10.3389/fmolb.2021.719678 | Indirect application relevance only; useful for contextualizing why conserved aldolases are studied. (pirovich2021multifunctionalfructose16bisphosphate pages 3-5) |
Table: This table summarizes the available evidence for the functional annotation of C. elegans aldo-1/P54216/T05D4.1, including identity mapping, enzymatic role, pathway context, regulatory patterns, phenotypes, and recent 2024 studies. It is useful as a citation-linked overview of what is directly supported by the retrieved snippets versus what remains inferred.
References
(pirovich2021multifunctionalfructose16bisphosphate pages 3-5): David B. Pirovich, Akram A. Da’dara, and Patrick J. Skelly. Multifunctional fructose 1,6-bisphosphate aldolase as a therapeutic target. Frontiers in Molecular Biosciences, Aug 2021. URL: https://doi.org/10.3389/fmolb.2021.719678, doi:10.3389/fmolb.2021.719678. This article has 111 citations.
(miersch2012sexdifferencesin pages 13-15): Claudia Miersch and Frank Döring. Sex differences in carbohydrate metabolism are linked to gene expression in caenorhabditis elegans. PLoS ONE, 7:e44748, Sep 2012. URL: https://doi.org/10.1371/journal.pone.0044748, doi:10.1371/journal.pone.0044748. This article has 25 citations and is from a peer-reviewed journal.
(umair2021teladorsagiacircumcincta16bisphosphate pages 4-8): Saleh Umair, Charlotte Bouchet, Nikola Palevich, and Heather Simpson. Teladorsagia circumcincta 1,6-bisphosphate aldolase: molecular and biochemical characterisation, structure analysis and recognition by immune hosts. Parasitologia, 1:1-11, Jan 2021. URL: https://doi.org/10.3390/parasitologia1010001, doi:10.3390/parasitologia1010001. This article has 3 citations.
(pujol2013succinatedehydrogenaseupregulation pages 2-4): Claire Pujol, Ivana Bratic-Hench, Marija Sumakovic, Jürgen Hench, Arnaud Mourier, Linda Baumann, Victor Pavlenko, and Aleksandra Trifunovic. Succinate dehydrogenase upregulation destabilize complex i and limits the lifespan of gas-1 mutant. PLoS ONE, 8:e59493, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0059493, doi:10.1371/journal.pone.0059493. This article has 45 citations and is from a peer-reviewed journal.
(weng2024malespecificbehavioraland pages 7-9): Yifei Weng and Coleen T. Murphy. Male-specific behavioral and transcriptomic changes in aging c. elegans neurons. iScience, 27:109910, Jun 2024. URL: https://doi.org/10.1016/j.isci.2024.109910, doi:10.1016/j.isci.2024.109910. This article has 10 citations and is from a peer-reviewed journal.
(feng2024transcriptomeanalysesdescribe pages 4-5): Dingxia Feng, Long Qu, and Jo Anne Powell-Coffman. Transcriptome analyses describe the consequences of persistent hif-1 over-activation in caenorhabditis elegans. PLOS ONE, 19:e0295093, Mar 2024. URL: https://doi.org/10.1371/journal.pone.0295093, doi:10.1371/journal.pone.0295093. This article has 3 citations and is from a peer-reviewed journal.
(weng2024malespecificbehavioraland pages 9-12): Yifei Weng and Coleen T. Murphy. Male-specific behavioral and transcriptomic changes in aging c. elegans neurons. iScience, 27:109910, Jun 2024. URL: https://doi.org/10.1016/j.isci.2024.109910, doi:10.1016/j.isci.2024.109910. This article has 10 citations and is from a peer-reviewed journal.