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Requirements for the biogenesis of [2Fe-2S] proteins in the human and yeast cytosol
- The biogenesis of iron–sulfur (Fe/S) proteins entails the synthesis and trafficking of Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, the multiple steps of biogenesis are accomplished by complex protein machineries in both mitochondria and cytosol. The underlying biochemical pathways have been elucidated over the past decades, yet the mechanisms of cytosolic [2Fe-2S] protein assembly have remained ill-defined. Similarly, the precise site of glutathione (GSH) requirement in cytosolic and nuclear Fe/S protein biogenesis is unclear, as is the molecular role of the GSH-dependent cytosolic monothiol glutaredoxins (cGrxs). Here, we investigated these questions in human and yeast cells by various in vivo approaches. [2Fe-2S] cluster assembly of cytosolic target apoproteins required the mitochondrial ISC machinery, the mitochondrial transporter Atm1/ABCB7 and GSH, yet occurred independently of both the CIA system and cGrxs. This mechanism was strikinglyThe biogenesis of iron–sulfur (Fe/S) proteins entails the synthesis and trafficking of Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, the multiple steps of biogenesis are accomplished by complex protein machineries in both mitochondria and cytosol. The underlying biochemical pathways have been elucidated over the past decades, yet the mechanisms of cytosolic [2Fe-2S] protein assembly have remained ill-defined. Similarly, the precise site of glutathione (GSH) requirement in cytosolic and nuclear Fe/S protein biogenesis is unclear, as is the molecular role of the GSH-dependent cytosolic monothiol glutaredoxins (cGrxs). Here, we investigated these questions in human and yeast cells by various in vivo approaches. [2Fe-2S] cluster assembly of cytosolic target apoproteins required the mitochondrial ISC machinery, the mitochondrial transporter Atm1/ABCB7 and GSH, yet occurred independently of both the CIA system and cGrxs. This mechanism was strikingly different from the ISC-, Atm1/ABCB7-, GSH-, and CIA-dependent assembly of cytosolic–nuclear [4Fe-4S] proteins. One notable exception to this cytosolic [2Fe-2S] protein maturation pathway defined here was yeast Apd1 which used the CIA system via binding to the CIA targeting complex through its C-terminal tryptophan. cGrxs, although attributed as [2Fe-2S] cluster chaperones or trafficking proteins, were not essential in vivo for delivering [2Fe-2S] clusters to either CIA components or target apoproteins. Finally, the most critical GSH requirement was assigned to Atm1-dependent export, i.e. a step before GSH-dependent cGrxs function. Our findings extend the general model of eukaryotic Fe/S protein biogenesis by adding the molecular requirements for cytosolic [2Fe-2S] protein maturation.…
Autor*innen: | Joseph J. BraymerORCiD, Oliver StehlingORCiD, Martin Stümpfig, Ralf Rösser, Farah Spantgar, Catharina M. Blinn, Ulrich Mühlenhoff, Antonio J. PierikORCiD, Roland LillORCiD |
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Dokumenttyp: | Zeitschriftenartikel |
Veröffentlichungsform: | Verlagsliteratur |
Sprache: | Englisch |
Titel des übergeordneten Werkes (Englisch): | Proceedings of the National Academy of Sciences |
Jahr der Erstveröffentlichung: | 2024 |
Organisationseinheit der BAM: | 1 Analytische Chemie; Referenzmaterialien |
1 Analytische Chemie; Referenzmaterialien / 1.8 Umweltanalytik | |
4 Material und Umwelt | |
4 Material und Umwelt / 4.1 Biologische Materialschädigung und Referenzorganismen | |
Veröffentlichende Institution: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
Verlag: | Proceedings of the National Academy of Sciences |
Verlagsort: | Washington D.C. |
Jahrgang/Band: | 121 |
Ausgabe/Heft: | 21 |
Aufsatznummer: | e2400740121 |
Erste Seite: | 1 |
Letzte Seite: | 12 |
DDC-Klassifikation: | Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Sanitär- und Kommunaltechnik; Umwelttechnik |
Freie Schlagwörter: | Biokorrosion; Hydrogenasen Microbially Induced Corrosion |
Themenfelder/Aktivitätsfelder der BAM: | Umwelt |
Umwelt / Biokorrosion | |
DOI: | 10.1073/pnas.2400740121 |
URN: | urn:nbn:de:kobv:b43-602328 |
ISSN: | 0027-8424 |
Verfügbarkeit des Dokuments: | Datei für die Öffentlichkeit verfügbar ("Open Access") |
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |
Datum der Freischaltung: | 12.06.2024 |
Referierte Publikation: | Ja |
Datum der Eintragung als referierte Publikation: | 22.07.2024 |
Schriftenreihen ohne Nummerierung: | Wissenschaftliche Artikel der BAM |