Heme sensing and trafficking in fungi

Area of Science:

• Microbiology and Mycology
• Cell Biology
• Medical Mycology

Background:

• Fungal pathogens pose significant threats to human health, necessitating novel therapeutic strategies.
• Nutrient acquisition, particularly heme, is critical for fungal survival and virulence during infection.
• Understanding heme uptake and trafficking mechanisms is key to developing new antifungal treatments.

Purpose of the Study:

• To review and synthesize recent studies on fungal heme acquisition mechanisms.
• To highlight the role of genetically encoded biosensors in studying heme trafficking in vivo.
• To emphasize the importance of endomembrane trafficking, mitochondria, and vacuoles in fungal heme homeostasis.

Main Methods:

• Utilized genetically encoded biosensors for quantitative analysis of heme in subcellular compartments.
• Investigated the dynamics of heme trafficking in living fungal cells.
• Focused on model fungus *Saccharomyces cerevisiae* and pathogenic fungi *Candida albicans* and *Cryptococcus neoformans*.

Main Results:

• Biosensors have been successfully adapted for detecting heme in fungi, extending their utility beyond other metabolites.
• Endocytosis plays a significant role in the uptake of heme by pathogenic fungi.
• Membrane contact sites involving mitochondria, endoplasmic reticulum, and vacuoles are crucial for intracellular iron and heme trafficking.

Conclusions:

• Fungal heme acquisition is a complex process involving endocytosis and intricate intracellular trafficking pathways.
• The interplay between mitochondria, ER, and vacuoles is vital for managing intracellular heme.
• Targeting these heme acquisition and trafficking mechanisms presents a promising avenue for developing new antifungal therapies.