Figure 3.

Pathways involved in C. perfringens epsilon-toxin (ETX) intracellular action. ETX (PDB ID: 1UYJ) action involves binding to its receptor (ETX-r), such as the myelin and lymphocyte (MAL) protein. Neutral sphingomyelinase (nSMase) may be activated resulting in sphingomyelin (SM) hydrolysis and ceramide (CER) production, which would facilitate ETX oligomer formation. Oligomerization results in a heptameric pore that induces a rapid loss of iK⁺, entry of Cl⁻ and Na⁺ (not shown), followed later by an increase of iCa²⁺. ETX-affected cells also lose important coenzymes required for energy production, including NAD⁺, NADH and CoA, contributing the formation of the mitochondrial permeability transition pore (MPTP). This would facilitate the translocation of the apoptosis-inducing factor (AIF), a caspase independent cell death factor, from mitochondria to the nucleus. Dashed red arrows represent what is concluded and/or suggested by the current authors. A dashed black arrow shows direction of movement.