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.

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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.

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Study IDST003264
Study TitleSLC25A48 controls mitochondrial choline import and metabolism
Study SummaryCholine 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 NameVerkerke
First NameAnthony
Address330 Brookline Avenue, CLS 730
Emailaverkerk@bidmc.harvard.edu
Phone7159231910
Submit Date2024-04-29
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-06-20
Release Version1
Anthony Verkerke Anthony Verkerke
https://dx.doi.org/10.21228/M8QV5X
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genoptye
SA354252Serum_7Control
SA354253Serum_2Control
SA354254Serum_8Control
SA354255Serum_1Control
SA354256Serum_6Control
SA354257Serum_5Control
SA354258Serum_4Control
SA354259Serum_3Control
SA354260Serum_10SLC25A48-KO
SA354261Serum_11SLC25A48-KO
SA354262Serum_12SLC25A48-KO
SA354263Serum_13SLC25A48-KO
SA354264Serum_14SLC25A48-KO
SA354265Serum_15SLC25A48-KO
SA354266Serum_16SLC25A48-KO
SA354267Serum_9SLC25A48-KO
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.

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

Analysis:

Analysis ID:AN005348
Analysis Type:MS
Chromatography ID:CH004050
Num Factors:2
Num Metabolites:117
Units:Peak area
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