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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Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Genoytpe Treatment
SA090822KO_6DFA_01KO HADHA Control
SA090823KO_6DFA_03KO HADHA Control
SA090824KO_6DFA_02KO HADHA Control
SA090825MUT_6DFA_02_inj02MUT HADHA 10 Day Fatty Acid Supplementation
SA090826MUT_6DFA_02_inj03MUT HADHA 11 Day Fatty Acid Supplementation
SA090827MUT_12DFA_03MUT HADHA 12 Day Fatty Acid Supplementation
SA090828MUT_12DFA_01MUT HADHA 12 Day Fatty Acid Supplementation
SA090829MUT_12DFA_02MUT HADHA 12 Day Fatty Acid Supplementation
SA090830MUT_12DFA_04MUT HADHA 12 Day Fatty Acid Supplementation
SA090831MUT_6DFA_01_inj01MUT HADHA 6 Day Fatty Acid Supplementation
SA090832MUT_6DFA_01_inj02MUT HADHA 7 Day Fatty Acid Supplementation
SA090833MUT_6DFA_01_inj03MUT HADHA 8 Day Fatty Acid Supplementation
SA090834MUT_6DFA_02_inj01MUT HADHA 9 Day Fatty Acid Supplementation
SA090835WT_12DFA_04WT HADHA 12 Day Fatty Acid Supplementation
SA090836WT_12DFA_02WT HADHA 12 Day Fatty Acid Supplementation
SA090837WT_12DFA_01WT HADHA 12 Day Fatty Acid Supplementation
SA090838WT_12DFA_03WT HADHA 12 Day Fatty Acid Supplementation
Showing results 1 to 17 of 17