Iron‑sulfur cluster biogenesis and function in Apicomplexa parasites

• Published in: Biochimica et biophysica acta. Molecular cell research 2025-01, Vol.1872 (1), p.119876, Article 119876
• Main Authors: Renaud, Eléa A., Maupin, Ambre J.M., Besteiro, Sébastien
• Format: Article
• Language: English
• Subjects: Animals; Apicomplexa - genetics; Apicomplexa - metabolism; Apicoplasts - genetics; Apicoplasts - metabolism; Drug target; Humans; Iron-Sulfur Proteins - genetics; Iron-Sulfur Proteins - metabolism; Iron‑sulfur cluster; Metabolism; Mitochondria - genetics; Mitochondria - metabolism; Plasmodium; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Toxoplasma
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2024.119876

Iron‑sulfur cluster are ubiquitous and ancient protein cofactors that support a wide array of essential cellular functions. In eukaryotes, their assembly requires specific and dedicated machineries in each subcellular compartment. Apicomplexans are parasitic protists that are collectively responsible for a significant burden on the health of humans and other animals, and most of them harbor two organelles of endosymbiotic origin: a mitochondrion, and a plastid of high metabolic importance called the apicoplast. Consequently, apicomplexan parasites have distinct iron‑sulfur cluster assembly machineries located to their endosymbiotic organelles, as well as a cytosolic pathway. Recent findings have not only shown the importance of iron‑sulfur cluster assembly for the fitness of these parasites, but also highlighted parasite-specific features that may be promising for the development of targeted anti-parasitic strategies. [Display omitted] •Apicomplexans are prevalent and morbidity-causing parasites infecting humans.•Most apicomplexan parasites harbor three distinct FeS synthesis pathways.•The plastid-located pathway is absent from mammalian hosts and vital for parasites.•Parasite-specific features in FeS cluster genesis may yield promising drug targets.