Chemical proteomics for subcellular proteome analysis

Protein functions are tightly regulated by their subcellular localization and dynamic alteration. Chemical proteomics offers convenience and efficiency for profiling protein features in a native context. In this review, we summarize the recent progress of subcellular-compartment-focused chemical proteomics which do not rely on organelle fractionation. Organelle-specific activity-based protein profiling (ABPP) and engineered ascorbate peroxidase (APEX) have been developed for proteome analysis within organelles and even sub-organelles. In parallel, our lab designed organelle-localizable reactive molecules (ORMs) to selectively tag nuclear and mitochondrial proteins. ORMs-based proteomics is applicable to primary neurons and brain slices, as well as cultured cell lines. In addition, we invented a conditional proteomics approach to elucidate zinc homeostasis by labeling and identifying proteins localized in Zn2+-rich space of live cells.