Evolutionary conservation and in vitro reconstitution of microsporidian iron–sulfur cluster biosynthesis

Freibert, Sven‐Andreas; Goldberg, Alina V.; Hacker, Christian; Molik, Sabine; Dean, Paul; Williams, Tom A.; Nakjang, Sirintra; Long, Shaojun; Sendra, Kacper M; Bill, Eckhard; Heinz, Eva; Hirt, Robert P.; Lucocq, John M.; Embley, T. Martin; Lill, Roland

doi:10.1038/ncomms13932

Cited by 78 publications

(86 citation statements)

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“…One such biosynthetic system, the iron-sulfur (Fe/S) cluster biogenesis machinery, is a notable example of the protoeukaryote nucleocytoplasm having become obligately dependent on the symbiont-derived system. Almost all modern eukaryotes share a conserved 'iron-sulfur cluster' (ISC) system in the mitochondrial matrix comprising 18 proteins [65], the majority of which have alphaproteobacterial origins [66]. The ISC system not only serves to synthesize Fe/S clusters and attach them to mitochondrial apoproteins, but it is also essential for the synthesis of Fe/S clusters in cytosolic and nuclear Fe/S proteins involved in key pathways (e.g.…”

Section: Reviewmentioning

confidence: 99%

“…ribosome assembly and function, nuclear DNA replication and repair) [65]. The CIA system, responsible for cytosolic and nuclear Fe/S cluster biogenesis, depends on an unknown sulfur-containing factor produced by the ISC system that is transported across the inner mitochondrial membrane by Atm1, an ABC transporter of alphaproteobacterial origin [66]. As a result of its critical role, ISC is the only known mitochondrial biosynthetic pathway that is essential in yeast [65] and is a highly conserved system across eukaryotic diversity [66].…”

Section: Reviewmentioning

confidence: 99%

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The Origin and Diversification of Mitochondria

2017

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Mitochondria are best known for their role in the generation of ATP by aerobic respiration. Yet, research in the past half century has shown that they perform a much larger suite of functions and that these functions can vary substantially among diverse eukaryotic lineages. Despite this diversity, all mitochondria derive from a common ancestral organelle that originated from the integration of an endosymbiotic alphaproteobacterium into a host cell related to Asgard Archaea. The transition from endosymbiotic bacterium to permanent organelle entailed a massive number of evolutionary changes including the origins of hundreds of new genes and a protein import system, insertion of membrane transporters, integration of metabolism and reproduction, genome reduction, endosymbiotic gene transfer, lateral gene transfer and the retargeting of proteins. These changes occurred incrementally as the endosymbiont and the host became integrated. Although many insights into this transition have been gained, controversy persists regarding the nature of the original endosymbiont, its initial interactions with the host and the timing of its integration relative to the origin of other features of eukaryote cells. Since the establishment of the organelle, proteins have been gained, lost, transferred and retargeted as mitochondria have specialized into the spectrum of functional types seen across the eukaryotic tree of life.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

The Origin and Diversification of Mitochondria

2017

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“…In eukaryotes, these proteins have been thoroughly characterized in humans (for review, see Rouault and Maio 2017), yeast (for review, see Braymer and Lill 2017), and trypanosomes (Basu et al 2016). Recent reports have functionally characterized these proteins in other protists, including Blastocystis (Tsaousis et al 2012) and microsporidia (Freibert et al 2017;Goldberg et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Localization of Fe‐S Biosynthesis Machinery in Cryptosporidium parvum Mitosome

Miller

Jossé

Tsaousis

2018

J Eukaryotic Microbiology

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Cryptosporidium is a protozoan, apicomplexan, parasite that poses significant risk to humans and animals, as a common cause of potentially fatal diarrhea in immunodeficient hosts. The parasites have evolved a number of unique biological features that allow them to thrive in a highly specialized parasitic lifestyle. For example, the genome of Cryptosporidium parvum is highly reduced, encoding only 3,805 proteins, which is also reflected in its reduced cellular and organellar content and functions. As such, its remnant mitochondrion, dubbed a mitosome, is one of the smallest mitochondria yet found. While numerous studies have attempted to discover the function(s) of the C. parvum mitosome, most of them have been focused on in silico predictions. Here, we have localized components of a biochemical pathway in the C. parvum mitosome, in our investigations into the functions of this peculiar mitochondrial organelle. We have shown that three proteins involved in the mitochondrial iron‐sulfur cluster biosynthetic pathway are localized in the organelle, and one of them can functionally replace its yeast homolog. Thus, it seems that the C. parvum mitosome is involved in iron‐sulfur cluster biosynthesis, supporting the organellar and cytosolic apoproteins. These results spearhead further research on elucidating the functions of the mitosome and broaden our understanding in the minimalistic adaptations of these organelles.

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“…1 and 2) (2, 16). Mitochondria or the evolutionarily derived hydrogenosomes and mitosomes appear to be essential for biogenesis of all cellular Fe/S proteins (7,17,18). The only notable exception to this rule may be a newly characterized eukaryotic organism, which appears to be devoid of mitochondria (19).…”

Section: Ubiquitous Iron-sulfur Clusters and Their Synthesis: An Overmentioning

confidence: 99%

“…In keeping with the evolutionary origin of the mitochondrion, the eukaryotic ISC machinery is believed to have been inherited from an alphaproteobacterium (18), and hence many of the mitochondrial and bacterial ISC proteins are highly similar in both structure and function (20,21). In fact, the functional investigation of the mitochondrial ISC system has largely benefited from the progress made in studying the related bacterial system and vice versa (6,20,22).…”

Section: Ubiquitous Iron-sulfur Clusters and Their Synthesis: An Overmentioning

confidence: 99%

Iron–sulfur cluster biogenesis and trafficking in mitochondria

Braymer

Lill

2017

Journal of Biological Chemistry

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320

293

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The biogenesis of iron-sulfur (Fe/S) proteins in eukaryotes is a multistage, multicompartment process that is essential for a broad range of cellular functions, including genome maintenance, protein translation, energy conversion, and the antiviral response. Genetic and cell biological studies over almost 2 decades have revealed some 30 proteins involved in the synthesis of cellular [2Fe-2S] and [4Fe-4S] clusters and their incorporation into numerous apoproteins. Mechanistic aspects of Fe/S protein biogenesis continue to be elucidated by biochemical and ultrastructural investigations. Here, we review recent developments in the pursuit of constructing a comprehensive model of Fe/S protein assembly in the mitochondrion. Ubiquitous iron-sulfur clusters and their synthesis: an overviewIron-sulfur (Fe/S) 2 clusters are inorganic cofactors that are essential for the proper functioning of virtually all biological cells (1). The chemical versatility of these clusters is utilized in fundamental life processes such as energy production, metabolic conversions, DNA maintenance, gene expression regulation, protein translation, and the antiviral response ( Fig. 1) (2-4). In eukaryotes, Fe/S proteins are found in or associated with the mitochondrion, endoplasmic reticulum, cytosol, and the nucleus. These cofactors participate in electron transfer reactions, Lewis acid catalysis, transfer of sulfur atoms, or facilitating structural roles (5, 6). Although the activities of some Fe/S proteins are dispensable for cell survival under certain conditions, for example fungal Fe/S enzymes in the metabolism of amino acids, others such as Fe/S proteins involved in DNA maintenance or protein translation are essential for cell viability (Fig. 1). The growing number of diseases that implicate Fe/S proteins or their assembly factors illustrates the essentiality of the various functions of these protein cofactors (7-9). The phenotypes associated with these "Fe/S diseases" and the in vivo work in model systems such as Saccharomyces cerevisiae and human cell culture have led to a mechanistic model of eukaryotic Fe/S protein biogenesis, in which the sequence of events required for proper synthesis and trafficking of Fe/S clusters has been elucidated (2). This model has been invaluable to diagnosing new mitochondrial disorders, and its continued advancement will enhance the ability for early diagnosis (10 -13). The focus of this review will be on the latest developments of the functional and mechanistic aspects that have advanced the model of mitochondrial Fe/S protein biogenesis.Cells typically maintain a strict balance of iron and sulfide ion concentrations due to their damaging redox reactions when present in excess (14, 15). The cell also uses a complex biosynthetic system to ensure that the sometimes redox-sensitive and labile Fe/S clusters are assembled correctly, trafficked to specific target apoproteins, and remain protected during these processes. This cellular control is exemplified by the 18 known "Fe/S cluster assembly" (ISC) proteins...

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Evolutionary conservation and in vitro reconstitution of microsporidian iron–sulfur cluster biosynthesis

Cited by 78 publications

References 77 publications

The Origin and Diversification of Mitochondria

The Origin and Diversification of Mitochondria

Localization of Fe‐S Biosynthesis Machinery in Cryptosporidium parvum Mitosome

Iron–sulfur cluster biogenesis and trafficking in mitochondria

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