Shepherd 2023 J Am Chem Soc

Shepherd RE, Kreinbrink AC, Njimoh CL, Vali SW, Lindahl PA (2023) Yeast mitochondria import aqueous feII and, when activated for iron-sulfur cluster assembly, export or release low-molecular-mass iron and also export iron that incorporates into cytosolic proteins. https://doi.org/10.1021/jacs.2c13439

» J Am Chem Soc 145:13556-69. PMID: 37339084 Open Access

Shepherd Rachel E, Kreinbrink Alexia C, Njimoh Cybele Lemuh, Vali Shaik Waseem, Lindahl Paul A (2023) J Am Chem Soc

Abstract: Iron-sulfur cluster (ISC) assembly occurs in both mitochondria and cytosol. Mitochondria are thought to export a low-molecular-mass (LMM) iron and/or sulfur species which is used as a substrate for cytosolic ISC assembly. This species, called X-S or (Fe-S)_int, has not been directly detected. Here, an assay was developed in which mitochondria were isolated from ⁵⁷Fe-enriched cells and incubated in various buffers. Thereafter, mitochondria were separated from the supernatant, and both fractions were investigated by ICP-MS-detected size exclusion liquid chromatography. Aqueous ⁵⁴Fe^II in the buffer declined upon exposure to intact ⁵⁷Fe-enriched mitochondria. Some ⁵⁴Fe was probably surface-absorbed but some was incorporated into mitochondrial iron-containing proteins when mitochondria were activated for ISC biosynthesis. When activated, mitochondria exported/released two LMM nonproteinaceous iron complexes. One species, which comigrated with an Fe-ATP complex, developed faster than the other Fe species, which also comigrated with phosphorus. Both were enriched in ⁵⁴Fe and ⁵⁷Fe, suggesting that the added ⁵⁴Fe entered a pre-existing pool of ⁵⁷Fe, which was also the source of the exported species. When ⁵⁴Fe-loaded ⁵⁷Fe-enriched mitochondria were mixed with isolated cytosol and activated, multiple cytosolic proteins became enriched with Fe. No incorporation was observed when ⁵⁴Fe was added directly to the cytosol in the absence of mitochondria. This suggests that a different Fe source in mitochondria, the one enriched mainly with ⁵⁷Fe, was used to export a species that was ultimately incorporated into cytosolic proteins. Iron from buffer was imported into mitochondria fastest, followed by mitochondrial ISC assembly, LMM iron export, and cytosolic ISC assembly.

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2023-06