Cell-penetrating peptides are excluded from the mitochondrial matrix.
CPPs (cell-penetrating peptides) facilitate cellular uptake of covalently attached macromolecules, through an as yet controversial mechanism that either involves direct membrane passage or a type of endocytosis. We investigated the potential of the CPPs penetratin and Tat to act as mitochondria-targeting vectors by testing whether they were internalized by isolated mitochondria, and by mitochondria within cells in culture. We also tested peptides conjugated to the mitochondria-targeting moiety triphenylphosphonium. We found no evidence for mitochondrial uptake by penetratin, Tat or their triphenylphosphonium conjugates. This result suggests that CPPs are unsuitable as mitochondria-targeting vectors, and implies an endocytic mode of cellular uptake for CPPs.
Ross
M F
MF
MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK. mfr@mrc-dunn.cam.ac.uk
Murphy
M P
MP
D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004705:Endocytosis; D015696:Gene Products, tat / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D021381:Protein Transport
D015696:Gene Products, tat; D010455:Peptides