Summary of Study ST002068

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 PR001310. The data can be accessed directly via it's Project DOI: 10.21228/M8CT43 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 IDST002068
Study TitleMutant CHCHD10 causes an extensive metabolic rewiring that precedes OXPHOS dysfunction in a murine model of mitochondrial cardiomyopathy
Study SummaryMitochondrial cardiomyopathies are fatal diseases, with no effective treatment. Alterations of heart mitochondrial function activate the mitochondrial integrated stress response (ISRmt), a transcriptional program affecting cell metabolism, mitochondrial biogenesis, and proteostasis. In humans, mutations in CHCHD10, a mitochondrial protein with unknown function, were recently associated with dominant multi-system mitochondrial diseases, whose pathogenic mechanisms remain to be elucidated. Here, in CHCHD10 knock-in mutant mice, we identify an extensive cardiac metabolic rewiring triggered by proteotoxic ISRmt. The stress response arises early on, before the onset of bioenergetic impairments, triggering a switch from oxidative to glycolytic metabolism, enhancement of transsulfuration and one carbon (1C) metabolism, and widespread metabolic imbalance. In parallel, increased NADPH oxidases elicit antioxidant responses leading to heme depletion. As the disease progresses, the adaptive metabolic stress response fails, resulting in fatal cardiomyopathy. Our findings suggest that early interventions to counteract metabolic imbalance could ameliorate mitochondrial cardiomyopathy associated with proteotoxic ISRmt.
Weill Cornell Medicine
Last NameSouthwell
First NameNneka
Address407 E 61st St
Submit Date2022-01-27
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2022-02-14
Release Version1
Nneka Southwell Nneka Southwell application/zip

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

mb_sample_id local_sample_id Genotype Sex Age (d)
SA194656S125dMut_9CHCHD10 S55L+/- F 125
SA194657S125dMut_10CHCHD10 S55L+/- F 125
SA194658S125dMut_7CHCHD10 S55L+/- F 125
SA194659S125dMut_6CHCHD10 S55L+/- F 125
SA194660S225dMut_13CHCHD10 S55L+/- F 225
SA194661S225dMut_16CHCHD10 S55L+/- F 225
SA194662S75dMut_1CHCHD10 S55L+/- F 75
SA194663S75dMut_2CHCHD10 S55L+/- F 75
SA194664S125dMut_11CHCHD10 S55L+/- M 125
SA194665S125dMut_8CHCHD10 S55L+/- M 125
SA194666S225dMut_14CHCHD10 S55L+/- M 225
SA194667S225dMut_12CHCHD10 S55L+/- M 225
SA194668S225dMut_15CHCHD10 S55L+/- M 225
SA194669S75dMut_4CHCHD10 S55L+/- M 75
SA194670S75dMut_3CHCHD10 S55L+/- M 75
SA194671S75dMut_5CHCHD10 S55L+/- M 75
SA194672S125dCtrl_8WT F 125
SA194673S125dCtrl_6WT F 125
SA194674S225dCtrl_13WT F 225
SA194675S225dCtrl_12WT F 225
SA194676S75dCtrl_3WT F 75
SA194677S75dCtrl_2WT F 75
SA194678S125dCtrl_9WT M 125
SA194679S125dCtrl_10WT M 125
SA194680S125dCtrl_7WT M 125
SA194681S125dCtrl_11WT M 125
SA194682S225dCtrl_14WT M 225
SA194683S225dCtrl_16WT M 225
SA194684S225dCtrl_15WT M 225
SA194685S75dCtrl_4WT M 75
SA194686S75dCtrl_5WT M 75
SA194687S75dCtrl_1WT M 75
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