Mortalin in cell protection from immune attack

The complement system plays major roles in innate and adaptive immunity. Complement activation may proceed through the classical, lectin and alternative pathways that initiate assembly of the membranolytic C5b-9 complex, also known as the membrane attack complex or MAC. Insertion of the C5b-9 complex into target cells membrane is an important weapon the body uses to fight pathogenic microorganisms. However, in many diseases, the C5b-9 complexes are considered pathogenic and inflict damages to patients' organs. During antibody-based therapy, complement C5b-9 complexes penetrate the plasma membrane of antibody-coated cancer cells and facilitate cancer destruction and remission. Several resistance mechanisms protect cancer cells from complement-dependent cytotoxicity. We found that the mitochondrial hsp70 mortalin supports cancer evasion from cell death activated by C5b-9. The mechanism whereby mortalin is protecting cells is currently under investigation. Initial results indicate that mortalin promotes C5b-9 elimination from the cell surface. The plausible target proteins recognized by mortalin are the C8 and C9 components of the C5b-9 complex. Since mortalin expression is elevated in cancer, it is conceivable that mortalin poses an obstacle to antibody-based therapy and as such might be worth targeting.