Reference: Pandey AK, et al. (2019) Mitochondria export iron-sulfur and sulfur intermediates to the cytoplasm for iron-sulfur cluster assembly and tRNA thiolation in yeast. J Biol Chem 294(24):9489-9502

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Abstract


Iron-sulfur clusters are essential cofactors of proteins. In eukaryotes, iron-sulfur cluster biogenesis requires a mitochondrial iron-sulfur cluster machinery (ISC) and a cytoplasmic iron-sulfur protein assembly machinery (CIA). Here we used mitochondria and cytoplasm isolated from yeast cells, and [35S]cysteine to detect cytoplasmic Fe-35S cluster assembly on a purified apoprotein substrate. We showed that mitochondria generate an intermediate, called (Fe-S)int, needed for cytoplasmic iron-sulfur cluster assembly. The mitochondrial biosynthesis of (Fe-S)int required ISC components such as Nfs1 cysteine desulfurase, Isu1/2 scaffold, and Ssq1 chaperone. Mitochondria then exported (Fe-S)int via the Atm1 transporter in the inner membrane, and we detected (Fe-S)int in active form. When (Fe-S)int was added to cytoplasm, CIA utilized it for iron-sulfur cluster assembly without any further help from the mitochondria. We found that both iron and sulfur for cytoplasmic iron-sulfur cluster assembly originate from the mitochondria, revealing a surprising and novel mitochondrial role. Mitochondrial (Fe-S)int export was most efficient in the presence of cytoplasm containing an apoprotein substrate, suggesting that mitochondria respond to the cytoplasmic demand for iron-sulfur cluster synthesis. Of note, the (Fe-S)int is distinct from the sulfur intermediate called Sint, which is also made and exported by mitochondria but is instead used for cytoplasmic tRNA thiolation. In summary, our findings establish a direct and vital role of mitochondria in cytoplasmic iron-sulfur cluster assembly in yeast cells.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Pandey AK, Pain J, Dancis A, Pain D
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