Mistargeting

Mistargeting is the inappropriate localization of proteins or other macromolecules within a cell due to failures in targeting signals or trafficking pathways. In healthy cells, proteins are directed from the site of synthesis to specific compartments such as the nucleus, endoplasmic reticulum, mitochondria, chloroplasts, or peroxisomes. Mistargeting occurs when these routing cues are defective or ignored, causing the molecule to reside in the wrong compartment or to accumulate in the cytosol.

Causes of mistargeting include mutations in signal peptides or transit sequences, defects in translocons or receptor components that recognize targeting signals, and disruptions to chaperone systems that assist in proper folding and delivery. Environmental stress, alternative splicing, and changes in cellular state can also alter trafficking routes. In plants and other organisms, mistargeting can affect plastids or other organelles when transit peptides fail to direct proteins correctly.

Consequences range from reduced organelle function to broader cellular stress. Mislocalized proteins can impair metabolic pathways, provoke proteotoxic stress, and activate quality-control responses such as the unfolded protein response. Mistargeting is linked to disease in some contexts; for example, peroxisomal disorders involve failure to import enzymes into peroxisomes, with significant metabolic consequences.

Detection and study of mistargeting rely on imaging and biochemical approaches. Fluorescence microscopy using organelle-specific markers, subcellular fractionation followed by proteomics, and targeted reporters help determine protein localization. Bioinformatic predictions of targeting signals and experimental validation combine to map localization patterns.

See also: protein targeting, organelle biogenesis, signal peptide, transit peptide, peroxisomal disorders.