Catalase-dependent H₂O₂ consumption by cardiac mitochondria and redox-mediated loss in insulin signaling

We have recently demonstrated that catalase content in mouse cardiac mitochondria is selectively elevated in response to high dietary fat, a nutritional state associated with oxidative stress and loss in insulin signaling. Catalase and various isoforms of glutathione peroxidase and peroxiredoxin each catalyze the consumption of H₂O₂. Catalase, located primarily within peroxisomes and to a lesser extent mitochondria, has a low binding affinity for H₂O₂ relative to glutathione peroxidase and peroxiredoxin. As such, the contribution of catalase to mitochondrial H₂O₂ consumption is not well understood. In the current study, using highly purified cardiac mitochondria challenged with micromolar concentrations of H₂O₂, we found that catalase contributes significantly to mitochondrial H₂O₂ consumption. In addition, catalase is solely responsible for removal of H₂O₂ in nonrespiring or structurally disrupted mitochondria. Finally, in mice fed a high-fat diet, mitochondrial-derived H₂O₂ is responsible for diminished insulin signaling in the heart as evidenced by reduced insulin-stimulated Akt phosphorylation. While elevated mitochondrial catalase content (~50%) enhanced the capacity of mitochondria to consume H₂O₂ in response to high dietary fat, the selective increase in catalase did not prevent H₂O₂-induced loss in cardiac insulin signaling. Taken together, our results indicate that mitochondrial catalase likely functions to preclude the formation of high levels of H₂O₂ without perturbing redox-dependent signaling.