Summary of Study ST003264
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 PR002026. The data can be accessed directly via it's Project DOI: 10.21228/M8QV5X 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 | ST003264 |
| Study Title | SLC25A48 controls mitochondrial choline import and metabolism |
| Study Summary | Choline is an essential nutrient for cellular metabolism, including the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A critical step in choline catabolism is the mitochondrial import and synthesis of choline-derived methyl donors, such as betaine. However, the underlying mechanisms and the biological significance of mitochondrial choline metabolism remain poorly understood. Here, we report that a previously uncharacterized mitochondrial inner-membrane protein, SLC25A48, controls mitochondrial choline transport and catabolism in vivo. We show that SLC25A48 is highly expressed in brown adipose tissue and is required for whole-body cold tolerance, thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity. Choline uptake into the mitochondria via SLC25A48 facilitates the synthesis of betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased production of reactive oxygen species and imbalanced mitochondrial lipids. Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48 gene and cancer cells lacking SLC25A48 exhibited elevated oxidative stress and impaired cell proliferation. Together, the present study identified SLC25A48 as a mitochondrial carrier that mediates choline catabolism and plays a critical role in mitochondrial function and cell survival. |
| Institute | Harvard Medical School |
| Last Name | Verkerke |
| First Name | Anthony |
| Address | 330 Brookline Avenue, CLS 730 |
| averkerk@bidmc.harvard.edu | |
| Phone | 7159231910 |
| Submit Date | 2024-04-29 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-06-20 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002026 |
| Project DOI: | doi: 10.21228/M8QV5X |
| Project Title: | SLC25A48 controls mitochondrial choline import and metabolism |
| Project Summary: | Choline is an essential nutrient for cellular metabolism, including the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A critical step in choline catabolism is the mitochondrial import and synthesis of choline-derived methyl donors, such as betaine. However, the underlying mechanisms and the biological significance of mitochondrial choline metabolism remain poorly understood. Here, we report that a previously uncharacterized mitochondrial inner-membrane protein, SLC25A48, controls mitochondrial choline transport and catabolism in vivo. We show that SLC25A48 is highly expressed in brown adipose tissue and is required for whole-body cold tolerance, thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity. Choline uptake into the mitochondria via SLC25A48 facilitates the synthesis of betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased production of reactive oxygen species and imbalanced mitochondrial lipids. Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48 gene and cancer cells lacking SLC25A48 exhibited elevated oxidative stress and impaired cell proliferation. Together, the present study identified SLC25A48 as a mitochondrial carrier that mediates choline catabolism and plays a critical role in mitochondrial function and cell survival. |
| Institute: | Beth Israel Deaconess Medical Center |
| Last Name: | Verkerke |
| First Name: | Anthony |
| Address: | 330 Brookline Avenue, Boston, Massachusetts, 02215, USA |
| Email: | averkerk@bidmc.harvard.edu |
| Phone: | 7159231910 |
Subject:
| Subject ID: | SU003384 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Gender: | Male |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genoptye | Sample source |
|---|---|---|---|
| SA354252 | Serum_7 | Control | Serum |
| SA354253 | Serum_2 | Control | Serum |
| SA354254 | Serum_8 | Control | Serum |
| SA354255 | Serum_1 | Control | Serum |
| SA354256 | Serum_6 | Control | Serum |
| SA354257 | Serum_5 | Control | Serum |
| SA354258 | Serum_4 | Control | Serum |
| SA354259 | Serum_3 | Control | Serum |
| SA354260 | Serum_10 | SLC25A48-KO | Serum |
| SA354261 | Serum_11 | SLC25A48-KO | Serum |
| SA354262 | Serum_12 | SLC25A48-KO | Serum |
| SA354263 | Serum_13 | SLC25A48-KO | Serum |
| SA354264 | Serum_14 | SLC25A48-KO | Serum |
| SA354265 | Serum_15 | SLC25A48-KO | Serum |
| SA354266 | Serum_16 | SLC25A48-KO | Serum |
| SA354267 | Serum_9 | SLC25A48-KO | Serum |
| Showing results 1 to 16 of 16 |
Collection:
| Collection ID: | CO003377 |
| Collection Summary: | Standard chow fed mice were fasted for four hours prior to serum or tissue collection. |
| Sample Type: | Serum |
Treatment:
| Treatment ID: | TR003393 |
| Treatment Summary: | Samples are from wild-type or SLC25A48-KO male mice fed a standard chow diet. Mice were fasted for four hours prior to sample collection. |
Sample Preparation:
| Sampleprep ID: | SP003391 |
| Sampleprep Summary: | 10 µL serum was mixed with 90 µL extraction solvent of methanol: acetonitrile: water 40: 40: 20 at -20 ˚C, and then vigorously vortexed. All samples were then conditioned to -4 ˚C, and centrifuged at 16,000 rpm/min. The supernatant was transferred to LC-MS tubes for analysis. |
Combined analysis:
| Analysis ID | AN005348 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo Vanquish |
| Column | Waters XBridge BEH Amide XP (150 x 2.1mm, 2.5um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive HF |
| Ion Mode | UNSPECIFIED |
| Units | Peak area |
Chromatography:
| Chromatography ID: | CH004050 |
| Chromatography Summary: | Waters XBridge BEH Amide XP Column (150 x 2.1mm, 2.5um) with guard column (5mm x 2.1mm, 2.5 µm) |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters XBridge BEH Amide XP (150 x 2.1mm, 2.5um) |
| Column Temperature: | 4˚C |
| Flow Gradient: | 0 - 3 min, 100% B; 3.2 - 6.2 min, 90% B; 6.5 - 10.5 min, 80% B; 10.7 - 13.5 min, 70% B; 13.7 - 16 min, 45% B; and 16.5 - 22 min, 100% B |
| Flow Rate: | 0.3 mL/ min |
| Solvent A: | 95% Water, 5% Acetonitrile; 10 mM ammonium acetate and 10 mM ammonium hydroxide |
| Solvent B: | 20% Water, 80% Acetonitrile; 10 mM ammonium acetate and 10 mM ammonium hydroxide |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS005078 |
| Analysis ID: | AN005348 |
| Instrument Name: | Thermo Q Exactive HF |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The mass spectrometry used was Q Exactive HF (Thermo Fisher Scientific, San Jose, CA), and scanned from 70 to 1000 m/z with switching polarity. The resolution was 120,000. Metabolites were identified based on accurate mass and retention time using an in-house library, and the software used was EI-Maven (Elucidata, Cambridge, MA). |
| Ion Mode: | UNSPECIFIED |
