Summary of Study ST003589
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002219. The data can be accessed directly via it's Project DOI: 10.21228/M8SR8N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003589 |
| Study Title | Metabolomics of Drosophila melanogaster under manganese (Mn) exposure (head) |
| Study Type | untargeted metabolomics |
| Study Summary | Parkinson’s disease (PD) is the most common motor disorder, for which environmental factors such as manganese (Mn) exposure may play a major etiologic role. In this study, we aim to identify metabolic pathways related to Mn-induced parkinsonism and discover therapeutic targets for manganism and potentially for PD. We developed an in vivo model of acute Mn toxicity in male Drosophila melanogaster (0, 10, and 30 mM of Mn2+ for 10 days) to recapitulate PD hallmarks, spanning behavior (climbing, locomotor assay), histology (H&E staining of neurons, MitoTracker assay), and mitochondrial function (Seahorse assay). High-coverage metabolomics of flies were conducted at an earlier point of dosage (Day 5), to identify early biochemical modulators before motor symptoms surfaced. Fly heads and bodies were extracted and analyzed using liquid chromatography–quadrupole-orbitrap mass spectrometry, following informatics approaches for compound identification and pathway analysis. The uploaded is the untargeted metabolomics component which contains raw data, alignment tables, and associated method details. |
| Institute | Columbia University |
| Department | Department of Environmental Health Sciences |
| Laboratory | The Miller Lab |
| Last Name | Lai |
| First Name | Yunjia |
| Address | 630 West 168th Street, P&S 16-421, New York, NY 10032 |
| yunjia.lai@outlook.com | |
| Phone | 9194805489 |
| Submit Date | 2024-06-23 |
| Num Groups | 3 |
| Total Subjects | 150; five samples per group; 10 subjects per sample |
| Num Males | 150; five samples per group; 10 subjects per sample |
| Publications | Science Signaling |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-12-31 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002219 |
| Project DOI: | doi: 10.21228/M8SR8N |
| Project Title: | Biotin rescues manganese-induced parkinson's disease phenotypes and neurotoxicity |
| Project Type: | untargeted metabolomics |
| Project Summary: | Occupational exposure to manganese (Mn) induces manganism and has been widely linked as a contributing environmental factor to Parkinson's disease (PD), featuring dramatic signature overlaps between the two in motor symptoms and clinical hallmarks. However, the molecular mechanism underlying this link remains elusive, and for combating PD, effective mechanism-based therapies are lacking. Here, we developed an adult Drosophila model of Mn toxicity to recapitulate key Parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosomes and mitochondria. We performed global metabolomics on flies at an early toxicity stage and identified metabolism of the B vitamin, biotin (vitamin B7), as a master pathway underpinning Mn toxicity with systemic, body–brain increases in Mn-treated groups compared to the controls. Using BtndRNAi mutant flies, we show that biotin depletion exacerbates Mn-induced neurotoxicity, Parkinsonism, and mitochondrial dysfunction, while in Mn-exposed wildtype flies, biotin feeding dramatically ameliorates these pathophenotypes. We further show in human induced stem cells (iPSCs)-differentiated midbrain dopaminergic neurons that the supplemented biotin protects against Mn-induced neuronal loss, cytotoxicity, and mitochondrial dysregulation. Finally, human data profiling biotin-related proteins show for PD cases elevated levels of biotin transporters compared to healthy controls, suggesting a potential role of biotin metabolism in PD. Taken together, our findings identified the compensatory biotin pathway as a convergent, systemic driver of Mn toxicity and Parkinsonian pathology, providing a new basis for devising effective countermeasures against manganism and PD. |
| Institute: | Columbia University |
| Department: | Department of Environmental Health Sciences |
| Laboratory: | The Miller Lab |
| Last Name: | Lai |
| First Name: | Yunjia |
| Address: | 630 West 168th Street, P&S 16-421, New York, NY 10032 |
| Email: | yunjia.lai@outlook.com |
| Phone: | 9194805489 |
| Funding Source: | National Institutes of Health |
| Publications: | Science Signaling |
Subject:
| Subject ID: | SU003718 |
| Subject Type: | Insect |
| Subject Species: | Drosophila melanogaster |
| Taxonomy ID: | 7227 |
| Genotype Strain: | wild-type (red eye) |
| Age Or Age Range: | all adult: 5-20 days, depending on the experiments |
| Gender: | Male |
| Species Group: | Insects |
Factors:
Subject type: Insect; Subject species: Drosophila melanogaster (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA391608 | head_Neg_x3h5 | Mn, 10 mM |
| SA391609 | head_Neg_x3h4 | Mn, 10 mM |
| SA391610 | head_Neg_x3h3 | Mn, 10 mM |
| SA391611 | head_Neg_x3h2 | Mn, 10 mM |
| SA391612 | head_Neg_x3h1 | Mn, 10 mM |
| SA391613 | head_Pos_x3h1 | Mn, 10 mM |
| SA391614 | head_Pos_x3h2 | Mn, 10 mM |
| SA391615 | head_Pos_x3h3 | Mn, 10 mM |
| SA391616 | head_Pos_x3h4 | Mn, 10 mM |
| SA391617 | head_Pos_x3h5 | Mn, 10 mM |
| SA391618 | head_Pos_x1h2 | Mn, 30 mM |
| SA391619 | head_Neg_x1h5 | Mn, 30 mM |
| SA391620 | head_Neg_x1h4 | Mn, 30 mM |
| SA391621 | head_Neg_x1h3 | Mn, 30 mM |
| SA391622 | head_Neg_x1h2 | Mn, 30 mM |
| SA391623 | head_Pos_x1h1 | Mn, 30 mM |
| SA391624 | head_Pos_x1h3 | Mn, 30 mM |
| SA391625 | head_Neg_x1h1 | Mn, 30 mM |
| SA391626 | head_Pos_x1h4 | Mn, 30 mM |
| SA391627 | head_Pos_x1h5 | Mn, 30 mM |
| SA391628 | head_Pos_poolinj4 | Pooled QC |
| SA391629 | head_Neg_poolinj4 | Pooled QC |
| SA391630 | head_Neg_poolinj3 | Pooled QC |
| SA391631 | head_Neg_poolinj2 | Pooled QC |
| SA391632 | head_Neg_poolinj1 | Pooled QC |
| SA391633 | head_Pos_poolinj3 | Pooled QC |
| SA391634 | head_Pos_poolinj2 | Pooled QC |
| SA391635 | head_Pos_poolinj1 | Pooled QC |
| SA391636 | head_Neg_x2h4 | Vehicle |
| SA391637 | head_Neg_x2h3 | Vehicle |
| SA391638 | head_Pos_x2h2 | Vehicle |
| SA391639 | head_Pos_x2h1 | Vehicle |
| SA391640 | head_Neg_x2h2 | Vehicle |
| SA391641 | head_Neg_x2h1 | Vehicle |
| SA391642 | head_Pos_x2h3 | Vehicle |
| SA391643 | head_Pos_x2h4 | Vehicle |
| SA391644 | head_Pos_x2h5 | Vehicle |
| SA391645 | head_Neg_x2h5 | Vehicle |
| Showing results 1 to 38 of 38 |
Collection:
| Collection ID: | CO003711 |
| Collection Summary: | To capture basic biochemical changes, flies were beheaded at 5-day of Mn exposure with heads and bodies collected and snap-frozen separately; each group had five sample replicates, and each replicate sample contained ten heads/bodies. |
| Sample Type: | fly head |
| Collection Tube Temp: | -80 |
Treatment:
| Treatment ID: | TR003727 |
| Treatment Summary: | Fly crosses were conducted in a 25 °C incubator and aged at 25 °C for 5-20 days, depending on the experiments. The pan-neuronal driver nSyb-GAL4 was used to mediate the genetic knockdown of the btnd gene. Both the stocks for nSyb-GAL4 and UAS-Btnd RNAi were obtained from Bloomington Drosophila Stock Center (BDSC) (HMC05012; Bloomington #60020). For Mn treatment, 0, 10, and 30 mM of MnCl2 (#7773-01-5; Santa Cruz Biotechnology, Dallas, TX) was mixed in 3 mL of water, and the instant food for flies was made using this water. Biotin supplementation was performed as previously described (Lohr et al., 2020). Biotin was added to instant fly food (Carolina Biological, Burlington, NC) at a final concentration of 30 mM. Unless noted otherwise, male flies were used throughout the study. Lohr KM, Frost B, Scherzer C, Feany MB. Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33608-33618. doi: 10.1073/pnas.1922392117. Epub 2020 Dec 14. PMID: 33318181; PMCID: PMC7777082. |
Sample Preparation:
| Sampleprep ID: | SP003725 |
| Sampleprep Summary: | To capture basic biochemical changes, flies were beheaded at 5-day of Mn exposure with heads and bodies collected and snap-frozen separately; each group had five sample replicates, and each replicate sample contained ten heads/bodies. To extract metabolites, thawed heads and bodies were added with ice-cold methanol:H2O (2:1, v/v) solution pre-spiked with isotope-labeled internal standards alongside zirconium oxide beads (0.5 mm i.d., Yittria stabilized) (Next Advance, Troy, NY). Samples were touch vortexed for 30 sec, manually ground using sterile, disposable pestles (DWK Life Sciences, Millville, NJ), placed on a bead beater (Next Advance, Troy, NY) in a cold room for 5 mins at the maximum speed, and finally centrifuged at 18,000 × g for 10 mins. The supernatant was SpeedVac-dried and reconstituted into acetonitrile:H2O (2:98, v/v) upon instrumental analysis. |
Chromatography:
| Chromatography ID: | CH004476 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters ACQUITY UPLC HSS C18 (100 x 2.1mm,1.8um) |
| Column Temperature: | 40°C |
| Flow Gradient: | a 15-min gradient: 2% B, 0–1 min; 2 to 15% B, 1–3 min; 15 to 50% B, 3–6 min; 50 to 98% B, 6–7.5 min; 98% B, 7.5–11.5 min; 98 to 2% B, 11.5–11.6 min; 2% B, 11.6–15 min |
| Flow Rate: | 0.4 mL/min |
| Solvent A: | 100% Water; 0.1% formic acid |
| Solvent B: | 100% Acetonitrile; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN005893 |
| Analysis Type: | MS |
| Chromatography ID: | CH004476 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003589_AN005893_Results.txt |
| Units: | Peak intensity (area) |
| Analysis ID: | AN005894 |
| Analysis Type: | MS |
| Chromatography ID: | CH004476 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003589_AN005894_Results.txt |
| Units: | Peak intensity (area) |
