Complement triggers relocation of Mortalin/GRP75 from mitochondria to the plasma membrane

作者：Mazkereth Niv; Rocca Francesco; Schubert Jennifer Rose; Geisler Claudia; Hillman Yaron; Egner Alexander; Fishelson Zvi^*

来源：Immunobiology, 2016, 221(12): 1395-1406.

DOI：10.1016/j.imbio.2016.07.005

• C5b-9
• Complement resistance
• Mortalin
• Mitochondria
• Cell death
• STED-microscopy
• Nanoscopy

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 35 nm, 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.

• 出版日期2016-12