Retracing the evolution from antimicrobial to targeting peptides

We experimentally challenged the endosymbiotic hypothesis that organelle-targeting peptides derive from antimicrobial amphipathic peptides delivered by the host cell, to which organelle progenitors became resistant. To explore the molecular changes required to convert such antimicrobial peptides into bona fide organelle-targeting peptides, we expressed a set of 13 antimicrobial peptides of various origins in the green alga Chlamydomonas reinhardtii that serves as a model for both mitochondrial and chloroplast import. The peptides were modified to match distinctive features of mitochondrial and chloroplast targeting peptides, and we assessed their targeting potential by following the intracellular localization and maturation of a Venus fluorescent reporter used as cargo protein. We present a temporal evolutionary scenario that emphasizes the early contribution of exchanging Lysines with Arginines in the sequence of the antimicrobial peptide, the evolution of a processing site followed by the addition of unstructured sequence and protein interaction sites that allow the selective targeting to the chloroplast.

Hydrogen peroxide-responsive AIE probe for imaging-guided organelle targeting and photodynamic cancer cell ablation

Hydrogen peroxide (H2O2), as one kind of key reactive oxygen species (ROS), is mainly produced endogenously primarily in the mitochondria. The selective monitoring of H2O2 in living cells is of...

Tuning the Organelle Specificity and Cytotoxicity of Iridium(III) Photosensitisers for Enhanced Phototheranostic Applications

Luminescent cyclometallated iridium(III) complexes with a polyhedral oligomeric silsesquioxane (POSS) unit were designed as efficient imaging reagents and photosensitisers that displayed tuneable organelle-targeting properties, minimal dark cytotoxicity and substantial photocytotoxicity...

All-in-one mitochondria-targeted NIR-II fluorophores for cancer therapy and imaging

Small-molecule subcellular organelle-targeting theranostic probes are crucial for early disease diagnosis and treatment.