Mitochondrial superoxide radicals differentially affect muscle activity and neural function

Tanja Godenschwege, Renée Forde, Claudette P. Davis, Anirban Paul, Kristopher Beckwith, Atanu Duttaroy

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Cellular superoxide radicals (O2-) are mostly generated during mitochondrial oxygen metabolism. O2- serves as the raw material for many reactive oxygen species (ROS) members like H2O2 and OH.- radicals following its catalysis by superoxide dismutase (SOD) enzymes and also by autocatalysis (autodismutation) reactions. Mitochondrial ROS generation could have serious implications on degenerative diseases. In model systems overproduction of mitochondrial O2- resulting from the loss of SOD2 function leads to movement disorders and drastic reduction in life span in vertebrates and invertebrates alike. With the help of a mitochondrial SOD2 loss-of-function mutant, Sod2n283, we measured the sensitivity of muscles and neurons to ROS attack. Neural outputs from flight motor neurons and sensory neurons were unchanged in Sod2n283 and the entire neural circuitry between the giant fiber (GF) and the dorsal longitudinal muscles (DLM) showed no overt defect due to elevated ROS. Such insensitivity of neurons to mitochondrial superoxides was further established through neuronal expression of SOD2, which failed to improve survival or locomotive ability of Sod2n283. On the other hand, ultrastructural analysis of Sod2n283 muscles revealed fewer mitochondria and reduced muscle ATP production. By targeting the SOD2 expression to the muscle we demonstrate that the early mortality phenotype of Sod2 n283 can be ameliorated along with signs of improved mobility. In summary, muscles appear to be more sensitive to superoxide attack relative to the neurons and such overt phenotypes observed in SOD2-deficient animals can be directly attributed to the muscle.

Original languageEnglish (US)
Pages (from-to)175-184
Number of pages10
JournalGenetics
Volume183
Issue number1
DOIs
StatePublished - Sep 2009

All Science Journal Classification (ASJC) codes

  • Genetics

Fingerprint Dive into the research topics of 'Mitochondrial superoxide radicals differentially affect muscle activity and neural function'. Together they form a unique fingerprint.

Cite this