Do fungi also undergo "ferroptosis"? A microscopic exploration of cellular death.

Abstract

Ferroptosis, a recently identified form of programmed cell death, has shown promising advancements in mammalian cell studies. However, research on ferroptosis in fungi is still in its nascent stages, resulting in limited understanding of its regulatory mechanisms. Given the unique regulatory mechanisms of ferroptosis and its significant implications for fungal research, this review focuses on the regulatory mechanisms of fungal ferroptosis, highlighting key target proteins and potential intervention strategies. Furthermore, the interplay between fungal ferroptosis and organelles is examined, analyzing the molecular logic of organelle-mediated ferroptosis, including their core functions and mechanisms promoting or inhibiting ferroptosis. Based on these findings, potential antifungal agents targeting the fungal ferroptosis pathway are summarized, along with their primary target pathways, key target proteins, and mechanisms of action. We also discuss the main characteristics of fungal ferroptosis and provide perspectives on future research directions. This review aims to provide new insights into the in-depth study of fungal ferroptosis and the development and design of novel antifungal agents targeting fungal ferroptosis. For instance, targeting key proteins or signaling pathways related to fungal ferroptosis may lead to the design of more effective antifungal drugs, overcoming the drug resistance issues of various drug-resistant fungi in current clinical settings.