Graphical Abstract Highlights d Tumorigenesis depends on functional OXPHOS d OXPHOS-derived ATP is not required for tumor formation d DHODH-driven pyrimidine biosynthesis requires CoQ redoxcycling d CoQ redox-cycling via OXPHOS drives tumorigenesis through pyrimidine biosynthesis

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This paper reports the first database on antioxidants contained in fruits produced and consumed within the south Andes region of South America. The database ( www.portalantioxidantes.com ) contains over 500 total phenolics (TP) and ORAC values for more than 120 species/varieties of fruits. All analyses were conducted by a single ISO/IEC 17025-certified laboratory. The characterization comprised native berries such as maqui ( Aristotelia chilensis ), murtilla ( Ugni molinae ), and calafate ( Barberis microphylla ), which largely outscored all other studied fruits. Major differences in TP and ORAC were observed as a function of the fruit variety in berries, avocado, cherries, and apples. In fruits such as pears, apples, apricots, and peaches, a significant part of the TP and ORAC was accounted for by the antioxidants present in the peel. These data should be useful to estimate the fruit-based intake of TP and, through the ORAC data, their antioxidant-related contribution to the diet of south Andes populations.

Deferoxamine (DFO) represents a widely used iron chelator for the treatment of iron overload. Here we describe the use of mitochondrially targeted deferoxamine (mitoDFO) as a novel approach to preferentially target cancer cells. The agent showed marked cytostatic, cytotoxic, and migrastatic properties in vitro, and it significantly suppressed tumor growth and metastasis in vivo. The underlying molecular mechanisms included (i) impairment of iron-sulfur [Fe-S] cluster/heme biogenesis, leading to destabilization and loss of activity of [Fe-S] cluster/heme containing enzymes, (ii) inhibition of mitochondrial respiration leading to mitochondrial reactive oxygen species production, resulting in dysfunctional mitochondria with markedly reduced supercomplexes, and (iii) fragmentation of the mitochondrial network and induction of mitophagy. Mitochondrial targeting of deferoxamine represents a way to deprive cancer cells of biologically active iron, which is incompatible with their proliferation and invasion, without disrupting systemic iron metabolism. Our findings highlight the importance of mitochondrial iron metabolism for cancer cells and demonstrate repurposing deferoxamine into an effective anticancer drug via mitochondrial targeting. Significance: These findings show that targeting the iron chelator deferoxamine to mitochondria impairs mitochondrial respiration and biogenesis of [Fe-S] clusters/heme in cancer cells, which suppresses proliferation and migration and induces cell death.