Ferroptosis-protective membrane domains in quiescence

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Quiescence is vital for stem cell maintenance and microbial survival but its regulation is poorly understood.
• Plasma membrane compartmentalization into microdomains is known, but its role in quiescence is unexplored.

Purpose of the Study:

• Investigate the role of plasma membrane compartmentalization in maintaining cellular quiescence.
• Identify mechanisms protecting quiescent cells from death, specifically ferroptosis.

Main Methods:

• Utilized yeast as a model organism.
• Investigated the function of flavodoxin-like proteins (FLPs) and eisosomes in quiescent cells.
• Analyzed lipid peroxidation, ferroptosis markers, and ubiquinol regeneration.

Main Results:

• Flavodoxin-like proteins (FLPs) within eisosomes protect quiescent cells from lipid peroxidation and ferroptosis.
• FLPs are essential for extramitochondrial ubiquinol regeneration, acting as antioxidants.
• Mutants lacking FLPs or eisosomes exhibit accelerated aging and impaired quiescence maintenance.

Conclusions:

• Plasma membrane compartmentalization, specifically eisosomes and FLPs, is critical for long-term quiescence survival.
• FLPs and glutathione peroxidases prevent iron-driven, PUFA-dependent ferroptotic cell death in yeast.
• This study reveals novel ferroptosis-protective mechanisms and highlights the importance of membrane organization in cellular longevity.