PNNL

Abstract

The SERCA2 isoform of the sarco/endoplasmic reticulum Ca2+-ATPase is sensitive to cellular conditions of inflammation and oxidative stress as evidenced by the common appearance of 3-nitrotyrosine modified forms of SERCA2 in aging and disease in both striated and smooth muscle of humans and several rodent models. Structural-functional studies of nitrated SERCA2 in aging heart and skeletal muscle demonstrate stoichiometric nitration of vicinal tyrosines, Tyr-294 and Tyr-295, on the lumenal side of the membrane-spanning helix, M4 that correlates with partial inhibition of its Ca2+-ATPase activity suggesting a possible regulatory function in down-regulating mitochondrial energy production and the associated generation of reactive oxygen/nitrogen species. This review discusses recent work regarding the nitrative and redox sensitivity of SERCA2 in muscle with respect to general cellular mechanisms of turnover and repair of modified proteins.