Fig. 9: The schematic representation illustrates how the disruption of the Erg11-Ncp1 interaction increases the sensitivity of azoles.

Ellipticine acts on Ncp1 to inhibit the Erg11-Ncp1 interaction within the ER, disrupting the electron transport chain between the two proteins. This disruption results in electron leakage, leading to the accumulation of excess electrons that react with oxygen to produce elevated levels of ROS. The surplus ROS oxidizes proteins synthesized in the ER, resulting in the production of misfolded proteins and the induction of ER stress. During ER stress, a substantial quantity of Ca²⁺ is transported from the ER to the cytoplasm, resulting in a notable elevation in cytoplasmic Ca²⁺ levels. The presence of a mitochondria-associated membrane (MAM) facilitates the transfer of Ca²⁺ from the ER to mitochondria. The buildup of Ca²⁺ in the mitochondria contributes to mitochondrial dysfunction and the advancement of cell apoptosis in C. albicans, thereby augmenting the efficacy of azoles.