title: Complement triggers relocation of Mortalin/GRP75 from mitochondria to the plasma membrane.
abstract: Mortalin/GRP75 is a ubiquitously expressed mitochondrial chaperon that is overexpressed in cancer. Mortalin protects cells from complement-dependent cytotoxicity (CDC) and facilitates elimination of the complement C5b-9 complexes from the cell surface. We performed a nanoscopical study aimed at imaging the distribution of the C5b-9 complexes in the plasma membrane and the postulated relocation of mortalin from the mitochondria to the plasma membrane. To gain a resolution of 35nm, the locations of the C5b-9 complex and mortalin were imaged with a STED (Stimulated Emission Depletion) microscope at sub-diffraction resolution. Early changes in the spatial distribution of the C5b-9 on the cell surface are described. Juxtaposition of the labeled mortalin and C5b-9 at the plasma membrane region within minutes after complement attack is evident. Microscopical analysis of the distribution of mortalin in the vicinity of the mitochondria of complement-treated cells shows a more diffused pattern relative to control cells, proposing exit of mortalin from the mitochondria in response to complement-induced stress. In support, analysis of cytoplasmic mortalin by immunoblotting shows enhanced level of mortalin in the cytoplasm in complement-treated cells. Our data demonstrates that cells can sense complement activation at the plasma membrane and in response, swiftly send mortalin to this region in order to deactivate it.
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Niv
authors.initials: N
authors.lastname: Mazkereth
authors.affiliation: Optical Nanoscopy, Laser-Laboratorium Göttingen e.V., D-37077 Göttingen, Germany.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rocca
authors.affiliation: Optical Nanoscopy, Laser-Laboratorium Göttingen e.V., D-37077 Göttingen, Germany.
authors.forename: Jennifer-Rose
authors.initials: JR
authors.lastname: Schubert
authors.affiliation: Optical Nanoscopy, Laser-Laboratorium Göttingen e.V., D-37077 Göttingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Hillman
authors.affiliation: Optical Nanoscopy, Laser-Laboratorium Göttingen e.V., D-37077 Göttingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Egner
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: lifish@post.tau.ac.il.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Fishelson
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism*; D036103:Nanotechnology; D009369:Neoplasms / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D015938:Complement Membrane Attack Complex; D018840:HSP70 Heat-Shock Proteins; C080352:mortalin
keywords: C5b-9; Cell death; Complement resistance; Mitochondria; Mortalin; Nanoscopy; STED-microscopy