Iron-loaded extracellular vesicles: angel or demon?

References

• Galaris D, Barbouti A, Pantopoulos K. Iron homeostasis and oxidative stress: an intimate relationship. Biochim Biophys Acta Mol Cell Res. 2019;1866(12):118535.
   PubMed Web of Science ®Google Scholar
• Brown CW, Amante JJ, Chhoy P, et al. Prominin2 drives ferroptosis resistance by stimulating iron export. Dev Cell. 2019;51(5):575–586.e4.
   PubMed Web of Science ®Google Scholar
• Todkar K, Chikhi L, Desjardins V, et al. Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs. Nat Commun. 2021;12(1):1971.
   PubMed Web of Science ®Google Scholar
• Hsu C, Morohashi Y, Yoshimura S, et al. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol. 2010;189(2):223–232.
   PubMed Web of Science ®Google Scholar
• Donovan A, Brownlie A, Zhou Y, et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature. 2000;403(6771):776–781.
   PubMed Web of Science ®Google Scholar
• Donovan A, Lima CA, Pinkus JL, et al. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 2005;1(3):191–200.
   PubMed Web of Science ®Google Scholar
• Li Y, Zeng X, Lu D, et al. Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis. Hum Reprod. 2021;36(4):951–964.
   PubMedGoogle Scholar
• Bao WD, Pang P, Zhou XT, et al. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease. Cell Death Differ. 2021;28(5):1548–1562.
   PubMed Web of Science ®Google Scholar
• Lakhal-Littleton S, Wolna M, Carr CA, et al. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function. Proc Natl Acad Sci U S A. 2015;112(10):3164–3169.
   PubMed Web of Science ®Google Scholar
• Billesbolle CB, Azumaya CM, Kretsch RC, et al. Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature. 2020;586(7831):807–811.
   PubMed Web of Science ®Google Scholar
• Schimanski LM, Drakesmith H, Merryweather-Clarke AT, et al. In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood. 2005;105(10):4096–4102.
   PubMedGoogle Scholar
• Truman-Rosentsvit M, Berenbaum D, Spektor L, et al. Ferritin is secreted via 2 distinct nonclassical vesicular pathways. Blood. 2018;131(3):342–352.
   PubMed Web of Science ®Google Scholar
• Hetet G, Devaux I, Soufir N, et al. Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations. Blood. 2003;102(5):1904–1910.
   PubMedGoogle Scholar
• Levi S, Cozzi A, Arosio P. Neuroferritinopathy: a neurodegenerative disorder associated with l-ferritin mutation. Best Pract Res Clin Haematol. 2005;18(2):265–276.
   PubMedGoogle Scholar
• Cohen LA, Gutierrez L, Weiss A, et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood. 2010;116(9):1574–1584.
   PubMed Web of Science ®Google Scholar
• Yanez-Mo M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
   PubMed Web of Science ®Google Scholar
• Yanatori I, Richardson DR, Dhekne HS, et al. CD63 is regulated by iron via the IRE-IRP system and is important for ferritin secretion by extracellular vesicles. Blood. 2021;138(16):1490–1503.
   PubMedGoogle Scholar
• Kimura T, Jia J, Kumar S, et al. Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy. EMBO J. 2017;36(1):42–60.
   PubMed Web of Science ®Google Scholar
• Sukseree S, Schwarze UY, Gruber R, et al. ATG7 is essential for secretion of iron from ameloblasts and normal growth of murine incisors during aging. Autophagy. 2020;16:1–7.
   PubMedGoogle Scholar
• El-Rifaie AA, Sabry D, Doss RW, et al. Heme oxygenase and iron status in exosomes of psoriasis patients. Arch Dermatol Res. 2018;310(8):651–656.
   PubMedGoogle Scholar
• Mackenzie K, Foot NJ, Anand S, et al. Regulation of the divalent metal ion transporter via membrane budding. Cell Discov. 2016;2:16011.
   PubMed Web of Science ®Google Scholar
• Meckes DG Jr., Gunawardena HP, Dekroon RM, et al. Modulation of B-cell exosome proteins by gamma herpesvirus infection. Proc Natl Acad Sci U S A. 2013;110(31):E2925–2933.
   PubMed Web of Science ®Google Scholar
• de Jong OG, Verhaar MC, Chen Y, et al. Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J Extracell Vesicles. 2012;2012:1.
   Google Scholar
• Rhodes MM, Koury ST, Kopsombut P, et al. Stress reticulocytes lose transferrin receptors by an extrinsic process involving spleen and macrophages. Am J Hematol. 2016;91(9):875–882.
   PubMedGoogle Scholar
• Datta A, Chen C, Gao YG, et al. Quantitative proteomics of medium-sized extracellular vesicle-enriched plasma of lacunar infarction for the discovery of prognostic biomarkers. Int J Mol Sci. 2022;23(19):11670.
   PubMedGoogle Scholar
• Valadi H, Ekstrom K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–659.
   PubMed Web of Science ®Google Scholar
• Kuang H, Dou G, Cheng L, et al. Humoral regulation of iron metabolism by extracellular vesicles drives antibacterial response. Nat Metab. 2023;5(1):111–128.
   PubMedGoogle Scholar
• Nakamura T, Naguro I, Ichijo H. Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases. Biochim Biophys Acta Gen Subj. 2019;1863(9):1398–1409.
   PubMed Web of Science ®Google Scholar
• Demaria M, O'Leary MN, Chang J, et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov. 2017;7(2):165–176.
   PubMed Web of Science ®Google Scholar
• Masaldan S, Clatworthy SAS, Gamell C, et al. Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis. Redox Biol. 2018;14:100–115.
   PubMed Web of Science ®Google Scholar
• Alibhai FJ, Lim F, Yeganeh A, et al. Cellular senescence contributes to age-dependent changes in circulating extracellular vesicle cargo and function. Aging Cell. 2020;19(3):e13103.
   PubMedGoogle Scholar
• Takasugi M, Okada R, Takahashi A, et al. Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nat Commun. 2017;8:15729.
   PubMed Web of Science ®Google Scholar
• Zou W, Lai M, Zhang Y, et al. Exosome release is regulated by mTORC1. Adv Sci. 2019;6(3):1801313.
   Web of Science ®Google Scholar
• Wang H, An P, Xie E, et al. Characterization of ferroptosis in murine models of hemochromatosis. Hepatology. 2017;66(2):449–465.
   PubMed Web of Science ®Google Scholar
• Mrowczynski OD, Madhankumar AB, Slagle-Webb B, et al. HFE genotype affects exosome phenotype in cancer. Biochim Biophys Acta Gen Subj. 2017;1861(8):1921–1928.
   PubMedGoogle Scholar
• Lee SY, Liu S, Mitchell RM, et al. HFE polymorphisms influence the response to chemotherapeutic agents via induction of p16INK4A. Int J Cancer. 2011;129(9):2104–2114.
   PubMedGoogle Scholar
• Mukherjee C, Kling T, Russo B, et al. Oligodendrocytes provide antioxidant defense function for neurons by secreting ferritin heavy chain. Cell Metab. 2020;32(2):259–272.e10.
   PubMedGoogle Scholar
• Gao H, Jin Z, Bandyopadhyay G, et al. Aberrant iron distribution via hepatocyte-stellate cell axis drives liver lipogenesis and fibrosis. Cell Metab. 2022;34(8):1201–1213.e5.
   PubMedGoogle Scholar
• Nie G, Sheftel AD, Kim SF, et al. Overexpression of mitochondrial ferritin causes cytosolic iron depletion and changes cellular iron homeostasis. Blood. 2005;105(5):2161–2167.
   PubMed Web of Science ®Google Scholar
• Shaw GC, Cope JJ, Li L, et al. Mitoferrin is essential for erythroid iron assimilation. Nature. 2006;440(7080):96–100.
   PubMed Web of Science ®Google Scholar
• Towers CG, Wodetzki DK, Thorburn J, et al. Mitochondrial-derived vesicles compensate for loss of LC3-mediated mitophagy. Dev Cell. 2021;56(14):2029–2042.e5.
   PubMed Web of Science ®Google Scholar
• Crewe C, Funcke JB, Li S, et al. Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes. Cell Metab. 2021;33(9):1853–1868.e11.
   PubMedGoogle Scholar
• Neuspiel M, Schauss AC, Braschi E, et al. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr Biol. 2008;18(2):102–108.
   PubMed Web of Science ®Google Scholar
• D'Acunzo P, Perez-Gonzalez R, Kim Y, et al. Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome. Sci Adv. 2021;7(7):eabe5085.
   PubMedGoogle Scholar
• Mathieu M, Martin-Jaular L, Lavieu G, et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17.
   PubMed Web of Science ®Google Scholar
• Choi DS, Kim DK, Kim YK, et al. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics. 2013;13(10–11):1554–1571.
   PubMed Web of Science ®Google Scholar
• Picca A, Guerra F, Calvani R, et al. Mitochondrial signatures in circulating extracellular vesicles of older adults with Parkinson’s disease: results from the EXosomes in PArkiNson’s disease (EXPAND) study. J Clin Med. 2020;9(2):504.
   PubMed Web of Science ®Google Scholar
• Sahoo S, Adamiak M, Mathiyalagan P, et al. Therapeutic and diagnostic translation of extracellular vesicles in cardiovascular diseases: roadmap to the clinic. Circulation. 2021;143(14):1426–1449.
   PubMedGoogle Scholar
• Joshi BS, de Beer MA, Giepmans BNG, et al. Endocytosis of extracellular vesicles and release of their cargo from endosomes. ACS Nano. 2020;14(4):4444–4455.
   PubMed Web of Science ®Google Scholar
• Atipimonpat A, Siwaponanan P, Khuhapinant A, et al. Extracellular vesicles from thalassemia patients carry iron-containing ferritin and hemichrome that promote cardiac cell proliferation. Ann Hematol. 2021;100(8):1929–1946.
   PubMed Web of Science ®Google Scholar
• van Meteren N, Lagadic-Gossmann D, Podechard N, et al. Extracellular vesicles released by polycyclic aromatic hydrocarbons-treated hepatocytes trigger oxidative stress in recipient hepatocytes by delivering iron. Free Radic Biol Med. 2020;160:246–262.
   PubMedGoogle Scholar
• Alkhateeb AA, Connor JR. The significance of ferritin in cancer: anti-oxidation, inflammation and tumorigenesis. Biochim Biophys Acta. 2013;1836(2):245–254.
   PubMed Web of Science ®Google Scholar
• Ito F, Kato K, Yanatori I, et al. Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin. Redox Biol. 2021;47:102174.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Zhao MF, Jiang S, et al. Liver governs adipose remodelling via extracellular vesicles in response to lipid overload. Nat Commun. 2020;11(1):719.
   PubMedGoogle Scholar
• Zhang Z, Funcke JB, Zi Z, et al. Adipocyte iron levels impinge on a fat-gut crosstalk to regulate intestinal lipid absorption and mediate protection from obesity. Cell Metab. 2021;33(8):1624–1639.e29.
   PubMedGoogle Scholar
• Jiang F, Chen Q, Wang W, et al. Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1. J Hepatol. 2020;72(1):156–166.
   PubMed Web of Science ®Google Scholar
• Wunderer F, Traeger L, Sigurslid HH, et al. The role of hepcidin and iron homeostasis in atherosclerosis. Pharmacol Res. 2020;153:104664.
   PubMedGoogle Scholar
• Gong L, Yu Q, Wang H, et al. Neurofilament light chain (NF-L) stimulates lipid peroxidation to neuronal membrane through microglia-derived ferritin heavy chain (FTH) secretion. Oxid Med Cell Longev. 2022;2022:3938940.
   PubMedGoogle Scholar
• Lee NJ, Ha SK, Sati P, et al. Potential role of iron in repair of inflammatory demyelinating lesions. J Clin Invest. 2019;129(10):4365–4376.
   PubMed Web of Science ®Google Scholar
• Lombardi M, Parolisi R, Scaroni F, et al. Detrimental and protective action of microglial extracellular vesicles on myelin lesions: astrocyte involvement in remyelination failure. Acta Neuropathol. 2019;138(6):987–1012.
   PubMed Web of Science ®Google Scholar
• Wang W, Knovich MA, Coffman LG, et al. Serum ferritin: past, present and future. Biochim Biophys Acta. 2010;1800(8):760–769.
   PubMed Web of Science ®Google Scholar