An mtDNA mutation accelerates liver aging by interfering with the ROS response and mitochondrial life cycle

作者：Niemann Jan; Johne Cindy; Schroeder Susanne; Koch Franziska; Ibrahim Saleh M; Schultz Julia; Tiedge Markus; Baltrusch Simone^*

来源：Free Radical Biology and Medicine, 2017, 102: 174-187.

DOI：10.1016/j.freeradbiomed.2016.11.035

• Aging
• Conplastic mice
• Liver
• Mitochondria
• Reactive oxygen species

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.

• 出版日期2017-1
• 单位河北医科大学