Neisserial PorB is translocated to the mitochondria of HeLa cells infected with Neisseria meningitidis and protects cells from apoptosis.
We have previously shown that purified meningococcal porin PorB associates with mitochondria and prevents apoptosis of B cells, Jurkat cells and HeLa cells (Massari et al., 2000, Proc Natl Acad Sci USA 97: 9070-9075). This work examines if intact meningococci have a similar effect as purified porins. It was first determined that intact live meningococci do not induce apoptosis of HeLa cells and do not perturb mitochondrial physiology. This latter consideration is important as Neisserial porins affect the susceptibility of cells to apoptosis by preventing mitochondrial depolarization and cytochrome c release, events involved in the apoptosis cascade. Purified PorB or PorB from live bacteria were found to translocate into and interact with mitochondria. It was then determined whether treatment of HeLa cells with meningococci could prevent staurosporine-mediated apoptosis due to an effect of PorB on the mitochondrial parameters. Incubation of HeLa cells with live meningococci prevented staurosporine-induced apoptosis, as ascertained by measurements of mitochondrial potential, translocation of mitochondrial cytochrome c to the cytosol, caspases activation, and nuclear DNA degradation. These data are consistent with our previous findings that purified PorB associates with mitochondria and prevents apoptosis, and demonstrates that the mechanism by which whole meningococci protects cells from apoptosis is a result of direct interaction of neisserial porin with mitochondria.
Massari
Paola
P
Department of Medicine, Boston University School of Medicine, 650 Albany St, Boston, MA 02118, USA.
King
Carol A
CA
Ho
Alan Yu
AY
Wetzler
Lee M
LM
D017209:Apoptosis; D001692:Biological Transport; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000378:metabolism / Q000472:pathogenicity*; D018272:Porins / Q000378:metabolism* / Q000494:pharmacology; D019311:Staurosporine / Q000037:antagonists & inhibitors; D014774:Virulence
D018272:Porins; C057699:porin protein, Neisseria; D019311:Staurosporine