Biogenesis of Iron–Sulfur Clusters and Their Role in DNA Metabolism

Abstract

Iron–sulfur (Fe/S) clusters (ISCs) are redox-active protein cofactors that their synthesis, transfer, and insertion into target proteins require many components. Mitochondrial ISC assembly is the foundation of all cellular ISCs in eukaryotic cells. The mitochondrial ISC cooperates with the cytosolic Fe/S protein assembly (CIA) systems to accomplish the cytosolic and nuclear Fe/S clusters maturation. ISCs are needed for diverse cellular functions, including nitrogen fixation, oxidative phosphorylation, mitochondrial respiratory pathways, and ribosome assembly. Recent research advances have confirmed the existence of different ISCs in enzymes that regulate DNA metabolism, including helicases, nucleases, primases, DNA polymerases, and glycosylases. Here we outline the synthesis of mitochondrial, cytosolic and nuclear ISCs and highlight their functions in DNA metabolism.

Recent Advances in the Elucidation of Frataxin Biochemical Function Open Novel Perspectives for the Treatment of Friedreich’s Ataxia

“…Fe-S clusters and heme are iron-containing protein cofactors providing enzymatic activities to a multitude of proteins involved in essential biological functions. Among the multifaceted functions of Fe-S proteins are electron transfer for ATP production in mitochondria ( Stiban et al, 2016 ) and DNA synthesis ( Zhang et al, 2014 ), redox catalysis in numerous metabolic pathways by the radical SAM superfamily ( Bauerle et al, 2015 ; Kimura and Suzuki, 2015 ), non-redox catalysis in the Krebs cycle ( Switzer, 1989 ; Stiban et al, 2016 ) and protein synthesis by ribosomes ( Kispal et al, 2005 ), iron donation ( Zhang et al, 2011 ), sulfur donation ( Lotierzo et al, 2005 ; Fugate and Jarrett, 2012 ; Mulliez et al, 2017 ), signaling ( Crack et al, 2014 ) and maintenance of genome integrity ( Fuss et al, 2015 ; Shi et al, 2021 ). Heme containing enzymes are also involved in electron transfer for ATP production ( Santucci et al, 2019 ), signaling ( Shimizu et al, 2019 ) and redox catalysis ( Flohé, 2020 ), but also oxygen transport ( Sen Gupta, 2019 ), xenobiotic detoxification ( Esteves et al, 2021 ) and oxidative stress defense ( Fugate and Jarrett, 2012 ; Aratani, 2018 ).…”

“…Further observations uncovered that abnormal frataxin production led to a marked decrease in enzymatic activities of mitochondrial and extra-mitochondrial iron-sulfur (Fe-S) cluster enzymes ( Foury and Cazzalini, 1997 ; Rotig et al, 1997 ; Wilson and Roof, 1997 ; Puccio et al, 2001 ; Duby et al, 2002 ; Muhlenhoff et al, 2002 ; Lu and Cortopassi, 2007 ; Martelli et al, 2007 ). Fe-S clusters are protein cofactors providing catalytic activities to numerous enzymes with essential functions in ATP production ( Stiban et al, 2016 ), Krebs cycle ( Switzer, 1989 ), redox catalysis ( Bauerle et al, 2015 ; Kimura and Suzuki, 2015 ), protein ( Kispal et al, 2005 ) and DNA ( Torrents et al, 2002 ; Zhang et al, 2011 , 2014 ) synthesis, signaling ( Crack et al, 2014 ) as well as DNA maintenance ( Fuss et al, 2015 ; Shi et al, 2021 ). Any defect in their biosynthesis thus lead to metabolic defects affecting energy production and many other cellular functions ( Beilschmidt and Puccio, 2014 ; Stehling et al, 2014 ; Alsina et al, 2018b ; Cardenas-Rodriguez et al, 2018 ).…”

Shared and host-specific transcriptomic response of Pseudomonas donghuensis P482 to the exudates of tomato (Dicot) and maize (Monocot) shed light on the host-adaptive traits in the promiscuous root colonizing bacteria

“…In Myxococcus , the action of TFP was found to be under the control of a chemotaxis-like system. It was postulated that the type IV pili are involved in directed cell movement, biofilm formation, guided tissue invasion, and other pathogenesis-related events (reviewed in: (89)).…”

“…Deleterious effects of NO result predominantly from the inactivation of proteins containing iron-sulfur (Fe-S) clusters (120, 121). Iron sulfur clusters are redox-active protein cofactors present in almost all organisms and required for many fundamental biochemical processes (89). In P482, we observed upregulation of proteins involved in the repair and the assembly of Fe-S clusters alongside those directly involved in NO detoxification.…”

“…Deleterious effects of NO result predominantly from the inactivation of proteins containing iron-sulfur (Fe-S) clusters (120,121). Iron sulfur clusters are redox-active protein cofactors present in almost all organisms and required for many fundamental biochemical processes (89).…”