Summary of Study ST001246

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000833. The data can be accessed directly via it's Project DOI: 10.21228/M8110J This work is supported by NIH grant, U2C- DK119886.


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 IDST001246
Study TitleTFPa/HADHA is required for fatty acid beta-oxidation and cardiolipin re-modeling in human cardiomyocytes (part-I)
Study SummaryMitochondrial trifunctional protein deficiency, due to mutations in hydratase subunit A (HADHA), results in sudden infant death syndrome (SIDS) with no cure. To reveal the disease etiology, we generated stem cell-derived cardiomyocytes from HADHA-deficient hiPSCs and accelerated their maturation via a novel, engineered MicroRNA Maturation Cocktail (MiMaC) that upregulated the epigenetic regulator, HOPX. Fatty acid challenged MiMaC treated HADHA mutant cardiomyocytes manifested the disease phenotype: defective calcium dynamics and repolarization kinetics which resulted in a pro-arrhythmic state. Single cell RNA-seq revealed a novel cardiomyocyte developmental intermediate, based on metabolic gene expression. This intermediate gave rise to mature-like cardiomyocytes in control cells but, mutant cells transitioned to a pathological state with reduced fatty acid beta-oxidation (FAO), reduced mitochondrial proton gradient, disrupted cristae structure and defective cardiolipin remodeling. This study reveals that TFPa/HADHA, a MLCL-AT-like enzyme, is required for FAO and cardiolipin remodeling, essential for functional mitochondria in human cardiomyocytes.
University of California, Davis
Last NameShowalter
First NameMegan
AddressUC Davis Genome Center, room 1313, 451 Health Sci Drive
Submit Date2019-08-26
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2019-09-06
Release Version1
Megan Showalter Megan Showalter application/zip

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Combined analysis:

Analysis ID AN002070
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Q Exactive HF Hybrid Quadrupole-Orbitrap
Column Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive HF hybrid Orbitrap
Units ng


Chromatography ID:CH001507
Chromatography Summary:Re-suspended samples were injected at 3 µL and 5 µL for ESI positive and negative modes respectively, onto a Waters Acquity UPLC CSH C18 (100 mm length × 2.1 mm id; 1.7 µm particle size) with an additional Waters Acquity VanGuard CSH C18 pre-column (5 mm × 2.1 mm id; 1.7 µm particle size) maintained at 65°C was coupled to a Vanquish UHPLC System. To improve lipid coverage, different mobile phase modifiers were used for positive and negative mode analysis 103. For positive mode 10 mM ammonium formate and 0.1% formic acid were used and 10 mM ammonium acetate (Sigma–Aldrich) was used for negative mode. Both positive and negative modes used the same mobile phase composition of (A) 60:40 v/v acetonitrile:water (LC-MS grade) and (B) 90:10 v/v isopropanol:acetonitrile. The gradient started at 0 min with 15% (B), 0–2 min 30% (B), 2–2.5 min 48% (B), 2.5–11 min 82% (B), 11–11.5 min 99% (B), 11.5–12 min 99% (B), 12–12.1 min 15% (B), and 12.1–15 min 15% (B). A flow rate of 0.6 mL/min was used.
Instrument Name:Thermo Q Exactive HF Hybrid Quadrupole-Orbitrap
Column Name:Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Column Temperature:65
Flow Gradient:0 min with 15% (B), 0-2 min 30% (B), 2-2.5 min 48% (B), 2.5-11 min 82% (B), 11-11.5 min 99% (B), 11.5-12 min 99% (B), 12-12.1 min 15% (B), and 12.1-15 min 15% (B)
Flow Rate:0.6ml/min
Solvent A:Pos mode:60% acetonitrile/40% water; 0.1% formic acid; 10 mM ammonium formate, Neg mode:60% acetonitrile/40% water; 0.1% formic acid; 10 mM ammonium acetate
Solvent B:Pos mode:90% isopropanol/10% acetonitrile; 0.1% formic acid; 10 mM ammonium formate,Neg mode:90% isopropanol/10% acetonitrile; 0.1% formic acid; 10 mM ammonium acetate
Chromatography Type:Reversed phase