A conditional proteomics approach to identify proteins involved in zinc homeostasis

Zinc signaling and dynamics play significant roles in many physiological responses and diseases. To understand the physiological roles of zinc in detail, comprehensive identification of proteins under high concentration of mobile zinc ion is crucial. We developed a 'conditional proteomics' approach to identify proteins involved in zinc homeostasis based on a chemical proteomic strategy that utilizes designer zinc-responsive labeling reagents to tag such proteins and quantitative mass spectrometry for their identification. We used this method to elucidate zinc dyshomeostasis induced by nitric-oxide-triggered oxidative stress in glioma cells, and we unveiled dynamic changes of the zinc-related proteomes. Moreover, we characterized unknown zinc-rich vesicles generated by oxidative stress as endoplasmic-reticulum- and Golgi-related vesicles.