Ferroptosis-protective membrane domains in quiescence
Amalia H. Megarioti,
Bianca M. Esch,
Alexandros Athanasopoulos,
Dimitrios Koulouris,
Manousos Makridakis,
Vasiliki Lygirou,
Martina Samiotaki,
Jerome Zoidakis,
Vicky Sophianopoulou,
Bruno André,
Florian Fröhlich,
Christos Gournas
Affiliations
Amalia H. Megarioti
Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications, National Center for Scientific Research ''Demokritos,” 15341 Agia Paraskevi, Greece; Department of Biology, National and Kapodistrian University of Athens, Panepistimioupolis, 15784 Athens, Greece
Bianca M. Esch
Bioanalytical Chemistry Section, Department of Biology/Chemistry, Osnabrück University, 49076 Osnabrück, Germany
Alexandros Athanasopoulos
Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications, National Center for Scientific Research ''Demokritos,” 15341 Agia Paraskevi, Greece
Dimitrios Koulouris
Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications, National Center for Scientific Research ''Demokritos,” 15341 Agia Paraskevi, Greece
Manousos Makridakis
Biotechnology Division, Systems Biology Center, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Vasiliki Lygirou
Biotechnology Division, Systems Biology Center, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Martina Samiotaki
Institute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming,” 16672 Vari, Greece
Jerome Zoidakis
Department of Biology, National and Kapodistrian University of Athens, Panepistimioupolis, 15784 Athens, Greece; Biotechnology Division, Systems Biology Center, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Vicky Sophianopoulou
Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications, National Center for Scientific Research ''Demokritos,” 15341 Agia Paraskevi, Greece
Bruno André
Molecular Physiology of the Cell Laboratory, Université Libre de Bruxelles (ULB), IBMM, 6041 Gosselies, Belgium
Florian Fröhlich
Bioanalytical Chemistry Section, Department of Biology/Chemistry, Osnabrück University, 49076 Osnabrück, Germany; Center for Cellular Nanoanalytic Osnabrück (CellNanOs), Osnabrück University, 49076 Osnabrück, Germany; Corresponding author
Christos Gournas
Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications, National Center for Scientific Research ''Demokritos,” 15341 Agia Paraskevi, Greece; Corresponding author
Summary: Quiescence is a common cellular state, required for stem cell maintenance and microorganismal survival under stress conditions or starvation. However, the mechanisms promoting quiescence maintenance remain poorly known. Plasma membrane components segregate into distinct microdomains, yet the role of this compartmentalization in quiescence remains unexplored. Here, we show that flavodoxin-like proteins (FLPs), ubiquinone reductases of the yeast eisosome membrane compartment, protect quiescent cells from lipid peroxidation and ferroptosis. Eisosomes and FLPs expand specifically in respiratory-active quiescent cells, and mutants lacking either show accelerated aging and defective quiescence maintenance and accumulate peroxidized phospholipids with monounsaturated or polyunsaturated fatty acids (PUFAs). FLPs are essential for the extramitochondrial regeneration of the lipophilic antioxidant ubiquinol. FLPs, alongside the Gpx1/2/3 glutathione peroxidases, prevent iron-driven, PUFA-dependent ferroptotic cell death. Our work describes ferroptosis-protective mechanisms in yeast and introduces plasma membrane compartmentalization as an important factor in the long-term survival of quiescent cells.