Organellar Maps Through Proteomic Profiling - A Conceptual Guide

Protein subcellular localization is highly regulated and critical for protein function. Spatial proteomics aims at capturing the localization dynamics of all proteins expressed in a given cell type. Among different approaches, organellar mapping through proteomic profiling stands out as the only method capable of determining the subcellular localizations of thousands of proteins in a single experiment. Importantly, it can also detect movements of proteins between subcellular compartments, providing an unbiased systems analysis tool for investigating physiological and pathological cellular processes.
Graphical Abstract Highlights Organelle profiling maps capture localizations of 1000s of proteins in one experiment. Comparing maps +/− perturbation reveals disease mechanisms & cellular responses. A conceptual guide to planning and interpreting organellar profiling experiments. A cross-study consensus set of human organellar marker proteins.
Protein subcellular localization is an essential and highly regulated determinant of protein function. Major advances in mass spectrometry and imaging have allowed the development of powerful spatial proteomics approaches for determining protein localization at the whole cell scale. Here, a brief overview of current methods is presented, followed by a detailed discussion of organellar mapping through proteomic profiling. This relatively simple yet flexible approach is rapidly gaining popularity, because of its ability to capture the localizations of thousands of proteins in a single experiment. It can be used to generate high-resolution cell maps, and as a tool for monitoring protein localization dynamics. This review highlights the strengths and limitations of the approach and provides guidance to designing and interpreting profiling experiments.