Abstract
Mitochondrial dysfunction affects liver metabolism, but it remains unclear whether this interferes with normal liver aging. We investigated several mitochondrial pathways in hepatocytes and liver tissue from a conplastic mouse strain compared with the control C57BL/6NTac strain over 18 months of life. The C57BL/6NTac-mtNODLtJ mice differed from C57BL/6NTac mice by a point mutation in mitochondrial-encoded subunit 3 of cytochrome c oxidase. Young C57BL/6NTac-mtNODLtJ mice showed reduced mitochondrial metabolism but similar reactive oxygen species (ROS) production to C57BL/6NTac mice. Whereas ROS increased almost equally up to 9 months in both strains, different mitochondrial adaptation strategies resulted in decreasing ROS in advanced age in C57BL/6NTac mice, but persistent ROS production in C57BL/6NTac-mtNODLtJ mice. Only the conplastic strain developed elongated mitochondrial networks with artificial loop structures, depressed autophagy, high mitochondrial respiration and up-regulated antioxidative response. Our results indicate that mtDNA mutations accelerate liver ballooning degeneration and carry a serious risk of premature organ aging.
| Original language | English |
|---|---|
| Journal | Free Radical Biology and Medicine |
| Volume | 102 |
| Pages (from-to) | 174-187 |
| Number of pages | 14 |
| ISSN | 0891-5849 |
| DOIs | |
| Publication status | Published - 01.01.2017 |
Funding
This work was supported by the BMBF GERONTOSYS 2 project ROSAge, the DFG ExC-306 (S.M. Ibrahim) and the DDG (S. Baltrusch). We are grateful to A. Kott, R. Waterstradt, S. Giers, I. Klamfuß and L. Wengler for technical assistance, to Dr. J. Brenmöhl (Leibniz Institute for Farm Animal Biology, Institute for Genome Biology, Dummerstorf, Germany) for help with the Seahorse XF Cell Mito Stress Test and to D. Beattie (freelance medical writer/UK) for editorial assistance.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
