FSP1 is a glutathione-independent ferroptosis suppressor

Ferroptosis is an iron-dependent form of necrotic cell death marked by oxidative damage to phospholipids1,2. To date, ferroptosis has been believed to be controlled only by the phospholipid hydroperoxide-reducing enzyme glutathione peroxidase 4 (GPX4)3,4 and radical-trapping antioxidants5,6. However, elucidation of the factors that underlie the sensitivity of a given cell type to ferroptosis7 is critical to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatment of cancer. Although metabolic constraints8 and phospholipid composition9,10 contribute to ferroptosis sensitivity, no cell-autonomous mechanisms have been identified that account for the resistance of cells to ferroptosis. Here we used an expression cloning approach to identify genes in human cancer cells that are able to complement the loss of GPX4. We found that the flavoprotein apoptosis-inducing factor mitochondria-associated 2 (AIFM2) is a previously unrecognized anti-ferroptotic gene. AIFM2, which we renamed ferroptosis suppressor protein 1 (FSP1) and which was initially described as a pro-apoptotic gene11, confers protection against ferroptosis elicited by GPX4 deletion. We further demonstrate that the suppression of ferroptosis by FSP1 is mediated by ubiquinone (also known as coenzyme Q10 (CoQ10)): the reduced form, ubiquinol, traps lipid peroxyl radicals that mediate lipid peroxidation, whereas FSP1 catalyses the regeneration of CoQ10 using NAD(P)H. Pharmacological targeting of FSP1 strongly synergizes with GPX4 inhibitors to trigger ferroptosis in a number of cancer entities. In conclusion, the FSP1–CoQ10–NAD(P)H pathway exists as a stand-alone parallel system, which co-operates with GPX4 and glutathione to suppress phospholipid peroxidation and ferroptosis

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Not AvailableStudy of genetic diversity and interspecific hybridizations plays an imperative role in the genetic improvement of crop plants. Microsatellite or simple sequence repeats (SSRs) markers have been the marker of choice for many genetic studies in perennial tree crops. In this study, genetic diversity of 23 cashew (Anacardium occidentale L.) germplasm accessions with unique traits was carried out using the cashew SSR (CSSR) markers. Besides, true hybridity of the interspecific hybrids of A. occidentale and A. microcarpum Ducke was investigated. Eight of the 21 CSSRs screened in 10 diverse accessions were polymorphic and used for genetic diversity analysis in 23 accessions. Major allele frequency ranged from 0.50 to 0.98; gene diversity ranged from 0.10 to 0.50, and polymorphism information content (PIC) ranged from 0.10 to 0.38 for the surveyed SSR loci. Dendrogram analysis of 23 accessions formed two main clusters with two sub-clusters in each. Clustering of the accessions had no relationship with the geographic region of collection. In tree hybridizations, early screening methods are becoming indispensable to ascertain the true hybridity of progenies to save the costs and resources. For the first time, three CSSR markers that detect the true hybridity of interspecific hybrids of cashew and its wild relative A. microcarpum were identified. Hybrid purity index of the progenies in interspecific crosses varied from 67 to 100%. These three CSSR markers capable of distinguishing the two Anacardium species could be useful in evolutionary studies involving these species and their natural hybrids in the wilds.Not Availabl