Divergent Molecular Evolution of the Mitochondrial Sulfhydryl:Cytochrome c Oxidoreductase Erv in Opisthokonts and Parasitic Protists

Eckers, Elisabeth; Petrungaro, Carmelina; Groß, Dominik P.; Riemer, Jan; Hell, Kai; Deponte, Marcel

doi:10.1074/jbc.m112.420745

Cited by 31 publications

(51 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result of general similarities between the phenotypes after the depletion of Atm1 and Erv1 in S. cerevisiae [20,21], we considered whether the massive mitochondrial swelling observed in T. brucei upon downregulation of TbErv1 [43] will also occur in the TbAtm-depleted cells. However, no alteration in organellar morphology was observed (data not shown), strongly indicating that the relationship between these proteins, in the marked absence of Mia40 [43,51], may be different in T. brucei. Both TbAtm and TbMdl contain a mitochondrial targeting sequence, transmembrane and nucleotide-binding domains, and have been previously found as components of the PS mitochondrial proteome [41].…”

Section: Discussionmentioning

confidence: 91%

Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe‐S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei

et al. 2015

View full text Add to dashboard Cite

ABC transporter mitochondrial 1 (Atm1) and multidrug resistance‐like 1 (Mdl) are mitochondrial ABC transporters. Although Atm1 was recently suggested to transport different forms of glutathione from the mitochondrion, which are used for iron‐sulfur (Fe‐S) cluster maturation in the cytosol, the function of Mdl remains elusive. In Trypanosoma brucei, we identified one homolog of each of these genes, TbAtm and TbMdl, which were downregulated either separately or simultaneously using RNA interference. Individual depletion of TbAtm and TbMdl led to limited growth defects. In cells downregulated for TbAtm, the enzymatic activities of the Fe‐S cluster proteins aconitase and fumarase significantly decreased in the cytosol but not in the mitochondrion. Downregulation of TbMdl did not cause any change in activities of the Fe‐S proteins. Unexpectedly, the simultaneous downregulation of TbAtm and TbMdl did not result in any growth defect, nor were the Fe‐S cluster protein activities altered in either the cytosolic or mitochondrial compartments. Additionally, TbAtm and TbMdl were able to partially restore the growth of the Saccharomyces cerevisiae Δatm1 and Δmdl2 null mutants, respectively. Because T. brucei completely lost the heme b biosynthesis pathway, this cofactor has to be obtained from the host. Based on our results, TbMdl is a candidate for mitochondrial import of heme b, which was markedly decreased in both TbMdl and TbAtm + TbMdl knockdowns. Moreover, the levels of heme a were strongly decreased in the same knockdowns, suggesting that TbMdl plays a key role in heme a biosynthesis, thus affecting the overall heme homeostasis in T. brucei.

show abstract

Section: Discussionmentioning

confidence: 91%

Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe‐S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Extant eukaryotes use complex protein import mechanisms to target nuclear encoded proteins to various mitochondrial compartments (Neupert & Herrmann, 2007), although more recent studies indicate that many microbial eukaryotes seem able to survive with simpler import mechanisms (Basu et al ., 2013; Burri et al ., 2006; Dagley et al ., 2009; Dolezal et al ., 2010; Eckers et al ., 2013). Significantly, evolution of mitochondrial targeting signals is not that difficult in terms of sequence evolution and synthetic evolution experiments suggest that such signals can arise readily, while selective pressure is likely greater for prevention of import of inappropriate polypeptides than for failure to translocate a bona fide mitochondrial protein (Allison & Schatz, 1986; Lemire et al ., 1989).…”

Section: Mitochondrial Origins and Lecamentioning

confidence: 99%

Molecular paleontology and complexity in the last eukaryotic common ancestor

Koumandou

Wickstead

Ginger

et al. 2013

Critical Reviews in Biochemistry and Molecular Biology

183

192

View full text Add to dashboard Cite

Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself.

show abstract

“…However, in the absence of most of these components in the Leishmania genome (Eckers et al ., ), this seems to be less likely. Nevertheless, as proposed recently (Eckers et al ., ), a ‘membrane‐association’ directed import of ARP1 could be a possibility, which needs to be further explored.…”

Section: Resultsmentioning

confidence: 99%

An actin‐like protein is involved in regulation of mitochondrial and flagellar functions as well as in intramacrophage survival of Leishmania donovani

Singh

Veluru

Trivedi

et al. 2014

Molecular Microbiology

View full text Add to dashboard Cite

SummaryActin-related proteins are ubiquitous actin-like proteins that show high similarity with actin in terms of their amino acid sequence and three-dimensional structure. However, in lower eukaryotes, such as trypanosomatids, their functions have not yet been explored. Here, we show that a novel actin-related protein (ORF LmjF.13.0950) is localized mainly in the Leishmania mitochondrion. We further reveal that depletion of the intracellular levels of this protein leads to an appreciable decrease in the mitochondrial membrane potential as well as in the ATP production, which appears to be accompanied with impairment in the flagellum assembly and motility. Additionally, we report that the mutants so generated fail to survive inside the mouse peritoneal macrophages. These abnormalities are, however, reversed by the episomal gene complementation. Our results, for the first time indicate that apart from their classical roles in the cytoplasm and nucleus, actin-related proteins may also regulate the mitochondrial function, and in case of Leishmania donovani they may also serve as the essential factor for their survival in the host cells.

show abstract

Divergent Molecular Evolution of the Mitochondrial Sulfhydryl:Cytochrome c Oxidoreductase Erv in Opisthokonts and Parasitic Protists

Cited by 31 publications

References 52 publications

Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe‐S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei

Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe‐S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei

Molecular paleontology and complexity in the last eukaryotic common ancestor

An actin‐like protein is involved in regulation of mitochondrial and flagellar functions as well as in intramacrophage survival of Leishmania donovani

Contact Info

Product

Resources

About