Reference - PMID:31040179 - Mitochondria export iron-sulfur and sulfur intermediates to the cytoplasm for iron-sulfur cluster assembly and tRNA thiolation in yeast.
Reference summary
- PubMed ID
- PMID:31040179
- Title
- Mitochondria export iron-sulfur and sulfur intermediates to the cytoplasm for iron-sulfur cluster assembly and tRNA thiolation in yeast.
- Authors
- Pandey AK, Pain J, Dancis A, Pain D
- Citation
- J Biol Chem 2019 Jun 14;294(24):9489-9502
- Publication year
- 2019
- 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 [ 35 S]cysteine to detect cytoplasmic Fe- 35 S 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 S int , 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.
