Malassezia species mitochondrial iron-dependent enzymes and intracellular iron pool (Malassezia iron metabolism)

Malassezia species are commensal lipophilic yeasts that inhabit human skin but can become pathogenic, leading to conditions such as seborrheic dermatitis and pityriasis versicolor. These fungi have an absolute requirement for iron to facilitate essential biological processes, including mitochondrial respiration, DNA replication, and the neutralization of reactive oxygen species. The target consists of the intracellular labile iron pool and various mitochondrial iron-dependent enzymes, such as cytochromes and iron-sulfur cluster proteins, which are critical for the fungal electron transport chain and overall metabolic viability (Leong et al., 2017, Medical Mycology). Antifungal agents like ciclopirox olamine target this system by acting as high-affinity chelators of polyvalent cations, specifically Fe3+. By sequestering iron, these drugs deplete the intracellular iron pool and inactivate essential iron-dependent enzymes, leading to the disruption of cellular metabolism and fungal cell death (Gupta & Plott, 2004, International Journal of Dermatology). This mechanism is distinct from the azole class of antifungals, which target ergosterol biosynthesis, making iron metabolism an effective alternative target for treating resistant Malassezia strains (Subissi et al., 2010, Drugs).

Other names

Malassezia iron-dependent enzymesMalassezia intracellular iron poolFungal iron-sulfur cluster proteinsMalassezia mitochondrial respiratory chain enzymes

Chelation of trivalent cations (Fe3+ and Al3+) leading to the depletion of the intracellular iron pool and subsequent inhibition of iron-dependent enzymes such as cytochromes, catalase, and peroxidase.