A peptide based on the pore-forming domain of pro-apoptotic poliovirus 2B viroporin targets mitochondria.
Non-structural poliovirus 2B protein induces plasma membrane permeabilization and has been recently implicated in triggering apoptosis via the mitochondrial pathway. Here we describe that the pore-forming P3 peptide, based on the 2B amphipathic domain, translocates through the plasma membrane of culture cells and targets mitochondria. Cell permeabilization by P3 versions of different lengths, together with peptide uptake analyses supported an internalization mechanism dependent on P3 capacity to interact physically with lipid bilayers and establish permeating pores therein. Internalized P3 was found associated with mitochondria, but contrary to the parental 2B protein, the short peptide did not affect the morphology or cell distribution of these organelles, nor induced apoptosis. We conclude that P3 constitutes a mitochondriotropic sequence, which is however devoid of 2B pro-apoptotic activity.
Madan
Vanesa
V
Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma de Madrid, Canto Blanco, 28049 Madrid, Spain.
Sánchez-Martínez
Silvia
S
Carrasco
Luis
L
Nieva
José L
JL
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism* / Q000821:virology; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017955:Poliovirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
C101758:2B protein, poliovirus; D008563:Membrane Lipids; D010455:Peptides; D017361:Viral Nonstructural Proteins