Summary of Study ST002315
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 PR001484. The data can be accessed directly via it's Project DOI: 10.21228/M8WT54 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 | ST002315 |
| Study Title | Differential requirements for mitochondrial electron transport chain components in the adult murine liver - in vivo glucose tracing |
| Study Summary | Wild-type and knockout mice (Ndufa9 and Cox10) were implanted with a jugular vein catheter and infused with [U-13C] glucose for 3 hours. Plasma and liver tissue was collected and analyzed via GCMS. |
| Institute | The University of Texas Southwestern Medical Center at Dallas |
| Department | Children's Research Institute |
| Laboratory | Prashant Mishra |
| Last Name | Lesner |
| First Name | Nicholas |
| Address | 6000 Harry Hines BLVD |
| nicholas.lesner@pennmedicine.upenn.edu | |
| Phone | 2146483784 |
| Submit Date | 2022-08-23 |
| Num Groups | 8 |
| Total Subjects | 60 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | GC-MS |
| Release Date | 2022-11-02 |
| Release Version | 1 |
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Project:
| Project ID: | PR001484 |
| Project DOI: | doi: 10.21228/M8WT54 |
| Project Title: | Differential requirements for mitochondrial electron transport chain components in the adult murine liver |
| Project Summary: | Mitochondrial electron transport chain (ETC) dysfunction due to mutations in the nuclear or mitochondrial genome is a common cause of metabolic disease in humans, and displays striking tissue specificity depending on the affected gene. The mechanisms underlying tissue specific phenotypes are not understood. Complex I (cI) is classically considered the entry point for electrons into the ETC, and in vitro experiments indicate that cI is required for basal respiration and maintenance of the NAD+/NADH ratio, an indicator of cellular redox status. This finding has largely not been tested in vivo. Here, we report that mitochondrial complex I (cI) is dispensable for homeostasis of the adult mouse liver; animals with hepatocyte-specific loss of cI function display no overt phenotypes or signs of liver damage, and maintain liver function, redox and oxygen status. Further analysis of cI-deficient livers did not reveal significant proteomic or metabolic changes, indicating little to no compensation is required in the setting of complex I loss. In contrast, complex IV (cIV) dysfunction in adult hepatocytes results in decreased liver function, impaired oxygen handling, steatosis, and liver damage, accompanied by significant metabolomic and proteomic perturbations. Metabolomic analysis suggests that the electron transfer flavoprotein complex constitutes a major route for electron entry into the hepatic ETC. Our results support a model whereby complex I loss is tolerated in the mouse liver because hepatocytes use alternative electron donors to fuel the mitochondrial ETC. |
| Institute: | The University of Texas Southwestern Medical Center at Dallas |
| Department: | Children's Research Institute |
| Laboratory: | Prashant Mishra |
| Last Name: | Lesner |
| First Name: | Nicholas |
| Address: | 6000 Harry Hines BLVD |
| Email: | nicholas.lesner@pennmedicine.upenn.edu |
| Phone: | 2146483784 |
