Biomedical subjects

Patricia L Dyal

Publications and source records attributed to Patricia L Dyal.

5 recordsLinked to original sources

PubMed2006

Hydrogenosomal succinyl-CoA synthetase from the rumen-dwelling fungus Neocallimastix patriciarum; an energy-producing enzyme of mitochondrial origin.

Hydrogenosomes are hydrogen-producing organelles that are related to mitochondria and found in a variety of evolutionarily unrelated anaerobic microbial eukaryotes. Similar to classic mitochondria, hydrogenosomes contain the enzyme catalyzing the only reaction of the citric acid cycle directly producing energy; succinyl-CoA synthetase. We have isolated and characterized the genes encoding both subunits of this enzyme from the anaerobic chytrid fungus Neocallimastix patriciarum, a model organism in hydrogenosome research. Both subunits contain all characteristic features of this enzyme, including predicted hydrogenosomal targeting signals. Phylogenetic analyses of succinyl-CoA synthetase clearly indicate its mitochondrial ancestry, both by affiliation with mitochondrially localized fungal homologues and by the sisterhood of the eukaryotic succinyl-CoA synthetase clade with alpha-proteobacteria. Our analyses of the Trichomonas vaginalis SCS sequences also confirmed the mitochondrial affiliation of these hydrogenosomal enzymes, in contrast to previous results. While both hydrogenosomal and mitochondrial succinyl-CoA synthetase homologues have been identified, no succinyl-CoA synthetase proteins were identifiable in taxa possessing another mitochondrially derived organelle, the mitosome. Our analyses further confirm the mitochondrial ancestry of the Neocallimastix hydrogenosome and sheds light upon the stepwise process by which mitochondria evolve into alternate forms of the organelle.

Amino Acid Sequence↗

PubMed2003

Fungal hydrogenosomes contain mitochondrial heat-shock proteins.

At least three groups of anaerobic eukaryotes lack mitochondria and instead contain hydrogenosomes, peculiar organelles that make energy and excrete hydrogen. Published data indicate that ciliate and trichomonad hydrogenosomes share common ancestry with mitochondria, but the evolutionary origins of fungal hydrogenosomes have been controversial. We have now isolated full-length genes for heat shock proteins 60 and 70 from the anaerobic fungus Neocallimastix patriciarum, which phylogenetic analyses reveal share common ancestry with mitochondrial orthologues. In aerobic organisms these proteins function in mitochondrial import and protein folding. Homologous antibodies demonstrated the localization of both proteins to fungal hydrogenosomes. Moreover, both sequences contain amino-terminal extensions that in heterologous targeting experiments were shown to be necessary and sufficient to locate both proteins and green fluorescent protein to the mitochondria of mammalian cells. This finding, that fungal hydrogenosomes use mitochondrial targeting signals to import two proteins of mitochondrial ancestry that play key roles in aerobic mitochondria, provides further strong evidence that the fungal organelle is also of mitochondrial ancestry. The extraordinary capacity of eukaryotes to repeatedly evolve hydrogen-producing organelles apparently reflects a general ability to modify the biochemistry of the mitochondrial compartment.

Amino Acid Sequence↗

PubMed2003

Mitochondria and hydrogenosomes are two forms of the same fundamental organelle.

Published data suggest that hydrogenosomes, organelles found in diverse anaerobic eukaryotes that make energy and hydrogen, were once mitochondria. As hydrogenosomes generally lack a genome, the conversion is probably one way. The sources of the key hydrogenosomal enzymes, pyruvate : ferredoxin oxidoreductase (PFO) and hydrogenase, are not resolved by current phylogenetic analyses, but it is likely that both were present at an early stage of eukaryotic evolution. Once thought to be restricted to a few unusual anaerobic eukaryotes, the proteins are intimately integrated into the fabric of diverse eukaryotic cells, where they are targeted to different cell compartments, and not just hydrogenosomes. There is no evidence supporting the view that PFO and hydrogenase originated from the mitochondrial endosymbiont, as posited by the hydrogen hypothesis for eukaryogenesis. Other organelles derived from mitochondria have now been described in anaerobic and parasitic microbial eukaryotes, including species that were once thought to have diverged before the mitochondrial symbiosis. It thus seems possible that all eukaryotes may eventually be shown to contain an organelle of mitochondrial ancestry, to which different types of biochemistry can be targeted. It remains to be seen if, despite their obvious differences, this family of organelles shares a common function of importance for the eukaryotic cell, other than energy production, that might provide the underlying selection pressure for organelle retention.

Anaerobiosis↗

PubMed2003

Hydrogenosomes, mitochondria and early eukaryotic evolution.

Available data suggest that unusual organelles called hydrogenosomes, that make ATP and hydrogen, and which are found in diverse anaerobic eukaryotes, were once mitochondria. The evolutionary origins of the enzymes used to make hydrogen, pyruvate:ferredoxin oxidoreductase (PFO) and hydrogenase, are unresolved, but it seems likely that both were present at an early stage of eukaryotic evolution. Once thought to be restricted to a few unusual anaerobes, these proteins are found in diverse eukaryotic cells, including our own, where they are targeted to different cell compartments. Organelles related to mitochondria and hydrogenosomes have now been found in species of anaerobic and parasitic protozoa that were previously thought to have separated from other eukaryotes before the mitochondrial endosymbiosis. Thus it is possible that all eukaryotes may eventually be shown to contain an organelle of mitochondrial ancestry, bearing testimony to the important role that the mitochondrial endosymbiosis has played in eukaryotic evolution. It remains to be seen if members of this family of organelles share a common function essential to the eukaryotic cell, that provides the underlying selection pressure for organelle retention under different living conditions.

Adenosine Triphosphate↗

PubMed2002

Conserved properties of hydrogenosomal and mitochondrial ADP/ATP carriers: a common origin for both organelles.

Mitochondria are one of the hallmarks of eukaryotic cells, exporting ATP in exchange for cytosolic ADP using ADP/ATP carriers (AAC) located in the inner mitochondrial membrane. In contrast, several evolutionarily important anaerobic eukaryotes lack mitochondria but contain hydrogenosomes, peculiar organelles of controversial ancestry that also supply ATP but, like some fermentative bacteria, make molecular hydrogen in the process. We have now identified genes from two species of the hydrogenosome-containing fungus Neocallimastix that have three-fold sequence repeats and signature motifs that, along with phylogenetic analysis, identify them as AACs. When expressed in a mitochondrial AAC- deficient yeast strain, the hydrogenosomal protein was correctly targeted to the yeast mitochondria inner membrane and yielded mitochondria able to perform ADP/ATP exchange. Characteristic inhibitors of mitochondrial AACs blocked adenine nucleotide exchange by the Neocallimastix protein. Thus, our data demonstrate that fungal hydrogenosomes and yeast mitochondria use the same pathway for ADP/ATP exchange. These experiments provide some of the strongest evidence yet that yeast mitochondria and Neocallimastix hydrogenosomes are but two manifestations of the same fundamental organelle.

Adenosine Diphosphate↗