Generation and bioenergetic analysis of cybrids containing mitochondrial DNA from mouse skeletal muscle during aging.
Mitochondrial respiratory chain defects have been associated with various diseases and normal aging, particularly in tissues with high energy demands including skeletal muscle. Muscle-specific mitochondrial DNA (mtDNA) mutations have also been reported to accumulate with aging. Our understanding of the molecular processes mediating altered mitochondrial gene expression to dysfunction associated with mtDNA mutations in muscle would be greatly enhanced by our ability to transfer muscle mtDNA to established cell lines. Here, we report the successful generation of mouse cybrids carrying skeletal muscle mtDNA. Using this novel approach, we performed bioenergetic analysis of cells bearing mtDNA derived from young and old mouse skeletal muscles. A significant decrease in oxidative phosphorylation coupling and regulation capacity has been observed with cybrids carrying mtDNA from skeletal muscle of old mice. Our results also revealed decrease growth capacity and cell viability associated with the mtDNA derived from muscle of old mice. These findings indicate that a decline in mitochondrial function associated with compromised mtDNA quality during aging leads to a decrease in both the capacity and regulation of oxidative phosphorylation.
Li
Youfen
Y
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Li
Hong-Zhi
HZ
Hu
Peiqing
P
Deng
Janice
J
Banoei
Mohammad Mehdi
MM
Sharma
Lokendra Kumar
LK
Bai
Yidong
Y
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019069:Cell Respiration; D002470:Cell Survival; D004272:DNA, Mitochondrial / Q000737:chemistry*; D006822:Hybrid Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption
D004272:DNA, Mitochondrial