Sod2 knockdown in the musculature has whole-organism consequences in Drosophila.
Oxidative damage to cell macromolecules by reactive oxygen species is associated with numerous diseases and aging. In Drosophila, RNAi-mediated silencing of the mitochondrial antioxidant manganese superoxide dismutase (SOD2) throughout the body dramatically reduces life span, accelerates senescence of locomotor function, and enhances sensitivity to applied oxidative stress. Here, we show that Sod2 knockdown in the musculature alone is sufficient to cause the shortened life span and accelerated locomotor declines observed with knockdown of Sod2 throughout the body, indicating that Sod2 deficiency in muscle is central to these phenotypes. Knockdown of Sod2 in the muscle also increased caspase activity (a marker for apoptosis) and caused a mitochondrial pathology characterized by swollen mitochondria, decreased mitochondrial content, and reduced ATP levels. These findings indicate that Sod2 plays a crucial role in the musculature in Drosophila and that the consequences of SOD2 loss in this tissue extend to the viability of the organism as a whole.
Martin
Ian
I
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23113, USA.
Jones
Melanie A
MA
Rhodenizer
Devin
D
Zheng
Jie
J
Warrick
John M
JM
Seroude
Laurent
L
Grotewiel
Mike
M
D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D055785:Gene Knockdown Techniques; D008931:Mitochondria, Muscle / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000235:genetics; D009043:Motor Activity / Q000235:genetics; D009132:Muscles / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
D000255:Adenosine Triphosphate; D020169:Caspases; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2