TY - JOUR
T1 - An mtDNA mutation accelerates liver aging by interfering with the ROS response and mitochondrial life cycle
AU - Niemann, Jan
AU - Johne, Cindy
AU - Schröder, Susanne
AU - Koch, Franziska
AU - Ibrahim, Saleh M.
AU - Schultz, Julia
AU - Tiedge, Markus
AU - Baltrusch, Simone
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85002050139&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2016.11.035
DO - 10.1016/j.freeradbiomed.2016.11.035
M3 - Journal articles
C2 - 27890640
AN - SCOPUS:85002050139
SN - 0891-5849
VL - 102
SP - 174
EP - 187
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -