Cytochrome c Oxidase Subunit VIII Mitochondrial Targeting Sequence (COX8 MTS)
The N-terminal mitochondrial targeting sequence (MTS) from human cytochrome c oxidase subunit VIII (COX8). Directs proteins to the mitochondrial matrix. First used for heterologous targeting by Rizzuto et al. (1992) and since adopted as the standard mitochondria-targeting sequence for engineered constructs.
Origin: Human cytochrome c oxidase subunit VIII (COX8, first 25 aa)
Characteristics
Amphipathic alpha-helix with net positive charge—characteristic of mitochondria-targeting peptides. Recognized by TOM/TIM import machinery. Cleaved by mitochondrial processing peptidase (MPP) after import, leaving the mature protein in the matrix. Fast and efficient in most mammalian cell types.
Applications: Mitochondria-targeted reporters, calcium sensors (e.g., mito-GCaMP), antioxidant enzymes, CRISPR tools for mitochondrial research. Standard sequence for any protein requiring mitochondrial matrix localization.
Limitations: Directs to the matrix specifically—not the inner membrane, intermembrane space, or outer membrane (those require different signals). Cleavage by MPP is context-dependent; verify mature protein size by western blot. May affect folding of some cargo proteins.
Sequence
References
- Rizzuto et al. (1992). Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin. J Cell Biol - Rizzuto 1992 COX8 MTS