Heat stress induces ferroptosis in a photosynthetic prokaryote

Abstract

Aguilera et al, show that ferroptosis, an oxidative and iron-dependent form of regulated cell death, plays an important role in the cyanobacterium Synechocystis sp.PCC 6803 in response to heat stress. AbstractFerroptosis is an oxidative and iron-dependent form of regulated cell death (RCD) recently described in eukaryotic organisms like animals, plants and parasites.Here we report that a similar process takes place in the photosynthetic prokaryote Synechocystis sp. PCC 6803 in response to heat stress. After a heat shock, Synechocystis PCC 6803 cells undergo a cell death pathway that can be suppressed by the canonical ferroptosis inhibitors, CPX or Fer-1, or by external addition of calcium (Ca ++ ), glutathione (GSH) or ascorbic acid (AsA). Moreover, as described for eukaryotic cells ferroptosis, this pathway is characterized by an early depletion of the antioxidants GSH and AsA, and by lipid peroxidation. In general, prokaryotes membranes contain poorly oxidizable saturated or monounsaturated lipid molecules, it was thought that free prokaryotes were not susceptible to ferroptosis but interestingly, that is not the case of cyanobacteria, which contain thylakoid membranes that are enriched in polyunsaturated-fatty-acid-containing phospholipids. These results indicate that all of the hallmarks described for eukaryotic ferroptosis are conserved in photosynthetic prokaryotes and suggest that ferroptosis might be an ancient cell death program.

Cell Death in Cyanobacteria: Current Understanding and Recommendations for a Consensus on Its Nomenclature

“…The pioneer reports inspired numerous subsequent studies, which were focused on RCD processes induced mainly in bloom-forming species subjected to harsh non-physiological treatments. These led to a significant body of literature describing cell death processes based on variable amounts of evidence and diagnostic markers, which have been named: “PCD,” “PCD-like,” “apoptosis,” “apoptotic-like,” “apoptosis-like PCD,” “autophagic-like,” “necrotic-like,” “autolytic-like,” and “ferroptosis-like” ( Figure 1 ; Table 1 ; Zheng et al, 2013 ; Yang et al, 2017 ; Aguilera et al, 2019 ; Hu and Rzymski, 2019 ).…”

“…This blue-fluorescent DNA stain enhances fluorescence upon binding to AT regions of dsDNA and is frequently used in animals to detect apoptosis ( Cummings et al, 2004 ). Taken together, to avoid misinterpretations and reach more accurate results, it is highly recommended to combine more than one assay to assess cell viability, for instance, we suggest the combination of fluorescent microscopy with SYTOX green and flow cytometry with FDA ( Aguilera et al, 2019 ).…”

“…PCC 73103 under nutrient limitation ( Fernández-Juárez et al, 2020 ), and in Synechocystis sp. PCC6803 when exposed to heat ( Aguilera et al, 2019 ). The data discussed above provide strong evidence for the participation of ROS in the signaling cascade, acting as a potential mediator in signal transduction pathways, as reported for eukaryotes ( Fleury et al, 2002 ; Achard et al, 2008 ; Newton et al, 2016 ).…”

“…Genes involved in glutathione synthesis ( gshA , ggt , and gpx2 ), and iron transporters ( feoB ) were induced after 50°C exposure in Synechocystis sp. PCC6803, suggesting that they are involved in the ferroptosis-like signaling pathway ( Aguilera et al, 2019 ).…”

“…Moreover, as described for ferroptosis in eukaryotic cells, the pathway in Synechocystis sp. PCC 6803 is characterized by lipid peroxidation and early depletion of the antioxidants GSH and AsA ( Aguilera et al, 2019 ). Thus, GSH depletion could be a potential hallmark to distinguish ferroptosis-like from other types of cell deaths ( Zhou et al, 2020 ).…”