Fungal mitochondrial inner membrane proteins

Fungal mitochondrial inner membrane proteins comprise a diverse set of enzymes and transporters essential for cellular respiration, energy production, and metabolic homeostasis in fungal pathogens. This group includes the electron transport chain (ETC) complexes, ATP synthase, and specialized enzymes such as dihydroorotate dehydrogenase (DHODH) and alternative oxidase (AOX). While some of these proteins are primary therapeutic targets for antifungal agents—such as DHODH for the novel drug olorofim—they are frequently identified as experimental off-targets in drug discovery and toxicology studies. For example, recent research has demonstrated that echinocandins like caspofungin can be sequestered in the mitochondrial inner membrane through high-affinity interactions with cardiolipin, which acts as a molecular sponge and reduces the drug's availability at its intended cell wall target. Furthermore, the high degree of conservation between certain fungal and human mitochondrial proteins poses a significant risk for host toxicity, making the selectivity of drugs targeting this compartment a critical challenge for clinical development.

Other names

Mitochondrial inner membrane proteinsMIM proteinsFungal respiratory chain proteinsFungal mitochondrial proteome

Inhibition of respiratory chain complexes, disruption of mitochondrial membrane potential, or sequestration of drug molecules within the mitochondrial compartment.