A cholesterol-dependent pore-forming toxin, which is a major virulence factor required for the escape of bacteria from phagosomal vacuoles and entry into the host cytosol. After binding to target membranes, the protein undergoes a major conformation change, leading to its insertion in the host membrane and formation of an oligomeric pore complex. Listeriolysin O activates mitogen-activated protein (MAP) kinase activity in host cells, most likely as a result of the permeabilization of the host cell membrane. Also induces a proteasome-independent degradation of UBE2I (the SUMO-conjugating enzyme UBC9) and a proteasome-dependent degradation of some sumoylated proteins. Finally, is necessary and sufficient for spacious Listeria-containing phagosomes (SLAPs) formation, suggesting a role for listeriolysin O in promoting L.monocytogenes replication in vacuoles, leading to persistent infection. Recognized by serum from healthy humans exposed to L.monocytogenes as well from patients who have recovered from listeriosis (PubMed:9284184). Activity of listeriolysin O is regulated on multiple levels. It should be high in the phagosome, thereby allowing escape of the bacteria from the phagosomal compartment. Then, once inside the host cytosol, the activity must be controlled to prevent lysis of the host plasma membrane and loss of the intracellular environment. Multiple regulatory mechanisms include translational repression, which is required to minimize levels of listeriolysin O in the host cytosol. In addition, cytolytic activity is pH-dependent. Activity is high in the acidic environment of the phagosome and is turned off in the neutral pH of the cytosol. Listeriolysin O is also ubiquitinated and rapidly degraded by host proteasome in cytosol. The lytic activity is activated by reducing agents and suppressed by oxidation. Also inhibited by very low amounts of cholesterol. Optimum pH is 5.5. Cytolytic activity is undetectable at pH 7.0. Homooligomeric pore complex of 35-50 subunits; when inserted in the host membrane. Secreted as soluble protein that then inserts into the host membrane and forms pores formed by transmembrane beta-strands. The N-terminal region is not required for secretion and hemolytic activity, but is involved in phagosomal escape of bacteria in infected cells and is critical for bacterial virulence. This region contains a PEST-like sequence, which does not mediate proteasomal degradation, but controls listeriolysin O production in the cytosol. Phosphorylated. Phosphorylation does not appear to be required for ubiquitination or degradation. Ubiquitinated. Cells lacking this gene have severely reduced cytokine production in the mouse Listeria-infected liver cells compared to wild-type. Belongs to the cholesterol-dependent cytolysin family. Extended N-terminus. Extended N-terminus.