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. 2021 Sep 29;18(6):1216–1239. doi: 10.1080/15548627.2021.1975914

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Figure 4. — ISC antagonizes FUNDC1-mediated mitophagy. ISC is mainly synthesized in mitochondria by the ISC assembly complex. The newly assembled ISC is transported into the cytosol to support the aconitase activity of ACO1/IRP1 for the TCA cycle. During iron deficiency or genetic susceptibility, defective ISC assembly enables ACO1/IRP1 unbound. The free ACO1/IRP1 targets to the IRE region of BCL2L1 mRNA, leading to the translational suppression and protein downregulation. The mitochondrial phosphatase PGAM5 is liberated to dephosphorylate FUNDC1 and facilitates mitophagy.