• The effect of cardiolipin acyl chain composition on cytochrome c protein conformation and resulting peroxidase activity: Exploring the potential mechanisms that contribute to cellular apoptosis.

      Wilkinson, Jennifer; Applied Health Sciences Program
      Skeletal muscle is a highly active tissue comprising up to 40% of total body weight. This highly dynamic tissue relies on mitochondria for calcium homeostasis, program cell death, and ATP production through mitochondrial respiration. The composition of mitochondrial phospholipids influences the functional efficiency of mitochondrial proteins, and healthy membranes include unsaturated acyl chains to promote respiration. Increasing membrane saturation has been implicated in muscle wasting, a condition caused by apoptosis and identified by the release of specific proteins from the mitochondria. It is unclear how membrane composition promotes the release of these pro-apoptotic proteins, specifically cytochrome c, to induce apoptosis. Thus, in this work synthetic membranes mimicking the composition of mitochondrial membranes from healthy and dystrophic mouse muscle were used. Cytochrome c conformation and function was measured with and without these membranes. There were no differences in protein conformation or function between the healthy and dystrophic membrane mimetics. However, cytochrome c affinity to these membranes was increased with greater unsaturation. This suggests that decreasing membrane saturation, as implicated in muscle wasting diseases, promotes the release of cytochrome c and apoptotic-mediated cell death. As such, interventions to improve or maintain membrane unsaturation may prove to be an alternative therapy for muscle wasting diseases.