Protein Tyrosine Nitration in the Mitochondria from Diabetic Mouse Heart

Abstract

Oxidative stress has been implicated in dysfunctional mitochondria indiabetes. Tyrosine nitration of mitochondrial proteins was observed underconditions of oxidative stress. We hypothesize that nitration of mitochondrialproteins is a common mechanism by which oxidative stress causes dysfunctionalmitochondria. The putative mechanism of nitration in a diabetic model ofoxidative stress and functional changes of nitrated proteins were studied inthis work. As a source of mitochondria, alloxan-susceptible andalloxan-resistant mice were used. These inbred strains are distinguished bythe differential ability to detoxify free radicals. A proteomic approachrevealed significant similarity between patterns of tyrosine-nitrated proteinsgenerated in the heart mitochondria under different andconditions of oxidative stress. This observation points to acommon nitrating species, which may derive from different nitrating pathwaysand may be responsible for the majority of nitrotyrosineformed. Functional studies show that protein nitration has an adverse effecton protein function and that protection against nitration protects functionalproperties of proteins. Because proteins that undergo nitration are involvedin major mitochondrial functions, such as energy production, antioxidantdefense, and apoptosis, we concluded that tyrosine nitration of mitochondrialproteins may lead to dysfunctional mitochondria in diabetes.