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Differential requirements for mitochondrial electron transport chain components in the adult murine liver
- Source :
- eLife, Vol 11 (2022)
- Publication Year :
- 2022
- Publisher :
- eLife Sciences Publications Ltd, 2022.
-
Abstract
- 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 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. 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.
- Subjects :
- mitochondria
liver
Complex I
Medicine
Science
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.bc53e8466ccf4687be0151852c83aa36
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.80919