Mitochondria function in cytoplasmic FeS protein biogenesis

Biochim Biophys Acta Mol Cell Res. 2024 Apr 17:119733. doi: 10.1016/j.bbamcr.2024.119733. Online ahead of print.ABSTRACTIron‑sulfur (FeS) clusters are cofactors of numerous proteins involved in various essential functions including cellular respiration, protein translation, DNA synthesis and repair, ribosome maturation, anti-viral responses, and isopropylmalate isomerase activity. Novel FeS cluster proteins are still being discovered due to the widespread use of cryogenic electron microscopy (cryo-EM) and elegant genetic screens targeted at protein discovery. A complex sequence of biochemical reactions mediated by a conserved machinery controls biosynthesis of FeS clusters. In eukaryotes, a remarkable epistasis has been observed: the mitochondrial machinery, termed ISC (Iron-Sulfur Cluster), lies upstream of the cytoplasmic machinery, termed CIA (Cytoplasmic Iron‑sulfur protein Assembly). The basis for this arrangement is the production of a hitherto uncharacterized intermediate, termed X-S or (FeS)int, produced in mitochondria by the ISC machinery, exported by the mitochondrial ABC transporter Atm1 (ABC7 in humans), and then utilized by the CIA machinery for the cytoplasmic/nuclear FeS cluster assembly. Genetic and biochemical findings supporting this sequence of events are herein presented. New structural views of the Atm1 transport phases are reviewed. The key compartmental roles of glutathione in cellular FeS cluster biogenesis are highlighted. Finally, data are prese...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Source Type: research