Modulation of ceramide-induced cell death and superoxide production by mitochondrial DNA-encoded respiratory chain defects in Rattus xenocybrid mouse cells
Ian A Trounce, Peter J Crouch, Kirstyn T Carey, Matthew McKenzie
Biochimica et Biophysica Acta. Bioenergetics | ELSEVIER SCIENCE BV | Published : 2013
Mitochondria play an integral role in cell death signaling, yet how mitochondrial defects disrupt this important function is not well understood. We have used a mouse L-cell fibroblast model harboring Rattus norvegicus mtDNA (Rn xenocybrids) to examine the effects of multiple oxidative phosphorylation (OXPHOS) defects on reactive oxygen species (ROS) generation and cell death signaling. Blue native-PAGE analyses of Rn xenocybrids revealed defects in OXPHOS complex biogenesis with reduced steady-state levels of complexes I, III and IV. Isolated Rn xenocybrid mitochondria exhibited deficiencies in complex II+III and III activities, with CIII-stimulated ROS generation 66% higher than in control..View full abstract
Awarded by National Health and Medical Research Council Australia
This work was supported by the Victorian Government's Operational Infrastructure Support Program, Monash Institute of Medical Research Start-up Funding (MMcK) and National Health and Medical Research Council Australia grants to IAT (Project Grant 145719) and MMcK (CDA Fellowship 541911). We thank Dick Cotton, Andrew Wilks and Mark Cook for support.