Dual Targeted Mitochondrial Proteins Are Characterized by Lower MTS Parameters and Total Net Charge

BACKGROUND: In eukaryotic cells, identical proteins can be located in different subcellular compartments (termed dual-targeted proteins). METHODOLOGY/PRINCIPAL FINDINGS: We divided a reference set of mitochondrial proteins (published single gene studies) into two groups: i) Dual targeted mitochondrial proteins and ii) Exclusive mitochondrial proteins. Mitochondrial proteins were considered dual-targeted if they were also found or predicted to be localized to the cytosol, the nucleus, the endoplasmic reticulum (ER) or the peroxisome. We found that dual localized mitochondrial proteins have i) A weaker mitochondrial targeting sequence (MitoProtII score, hydrophobic moment and number of basic residues) and ii) a lower whole-protein net charge, when compared to exclusive mitochondrial proteins. We have also generated an annotation list of dual-targeted proteins within the predicted yeast mitochondrial proteome. This considerably large group of dual-localized proteins comprises approximately one quarter of the predicted mitochondrial proteome. We supported this prediction by experimental verification of a subgroup of the predicted dual targeted proteins. CONCLUSIONS/SIGNIFICANCE: Taken together, these results establish dual targeting as a widely abundant phenomenon that should affect our concepts of gene expression and protein function. Possible relationships between the MTS/mature sequence traits and protein dual targeting are discussed.