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Gustavo Arrizabalaga - One of the best experts on this subject based on the ideXlab platform.
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identification of fis1 interactors in toxoplasma gondii reveals a novel protein required for peripheral distribution of the Mitochondrion
Mbio, 2020Co-Authors: Kylie Jacobs, Robert A. Charvat, Gustavo ArrizabalagaAbstract:ABSTRACT Toxoplasma gondii’s single Mitochondrion is very dynamic and undergoes morphological changes throughout the parasite’s life cycle. During parasite division, the Mitochondrion elongates, enters the daughter cells just prior to cytokinesis, and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular environment to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane and that this effect depends on the function of the fission-related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant-negative effect that affects the morphology of the Mitochondrion. As this suggests that Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner, we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the Mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite Mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1, the Mitochondrion is retracted away from the pellicle and instead is collapsed, as normally seen only in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth, and proper mitochondrial morphology is a prerequisite for mitochondrial division. IMPORTANCEToxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and congenitally infected. Current therapies are not effective against all life stages of the parasite, and many cause toxic effects. The single Mitochondrion of this parasite is a validated drug target, and it changes its shape throughout its life cycle. When the parasite is inside a cell, the Mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood and the proteins involved are currently not known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.
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Identification of Fis1 interactors in Toxoplasma gondii reveals a novel protein required for peripheral distribution of the Mitochondrion
bioRxiv, 2019Co-Authors: Kylie Jacobs, Robert A. Charvat, Gustavo ArrizabalagaAbstract:ABSTRACT Toxoplasma gondii’s singular Mitochondrion is very dynamic and undergoes morphological changes throughout the parasite’s life cycle. During parasite division, the Mitochondrion elongates, enters the daughter cells just prior to cytokinesis and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane, and that this effect depends on the function of the fission related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant negative effect that affects the morphology of the Mitochondrion. As this suggests Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the Mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite Mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1 the Mitochondrion is retracted away from the pellicle and instead is collapsed, as only normally seen in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth and proper mitochondrial morphology is a prerequisite for mitochondrial division. IMPORTANCE Toxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and the congenitally infected. Current therapies are not effective against all life stages of the parasite and many cause toxic effects. The single Mitochondrion of this parasite is a validated drug target and it changes its shape throughout its life cycle. When the parasite is inside of a cell, the Mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood nor are the proteins involved currently known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.
Kylie Jacobs - One of the best experts on this subject based on the ideXlab platform.
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identification of fis1 interactors in toxoplasma gondii reveals a novel protein required for peripheral distribution of the Mitochondrion
Mbio, 2020Co-Authors: Kylie Jacobs, Robert A. Charvat, Gustavo ArrizabalagaAbstract:ABSTRACT Toxoplasma gondii’s single Mitochondrion is very dynamic and undergoes morphological changes throughout the parasite’s life cycle. During parasite division, the Mitochondrion elongates, enters the daughter cells just prior to cytokinesis, and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular environment to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane and that this effect depends on the function of the fission-related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant-negative effect that affects the morphology of the Mitochondrion. As this suggests that Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner, we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the Mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite Mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1, the Mitochondrion is retracted away from the pellicle and instead is collapsed, as normally seen only in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth, and proper mitochondrial morphology is a prerequisite for mitochondrial division. IMPORTANCEToxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and congenitally infected. Current therapies are not effective against all life stages of the parasite, and many cause toxic effects. The single Mitochondrion of this parasite is a validated drug target, and it changes its shape throughout its life cycle. When the parasite is inside a cell, the Mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood and the proteins involved are currently not known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.
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Identification of Fis1 interactors in Toxoplasma gondii reveals a novel protein required for peripheral distribution of the Mitochondrion
bioRxiv, 2019Co-Authors: Kylie Jacobs, Robert A. Charvat, Gustavo ArrizabalagaAbstract:ABSTRACT Toxoplasma gondii’s singular Mitochondrion is very dynamic and undergoes morphological changes throughout the parasite’s life cycle. During parasite division, the Mitochondrion elongates, enters the daughter cells just prior to cytokinesis and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane, and that this effect depends on the function of the fission related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant negative effect that affects the morphology of the Mitochondrion. As this suggests Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the Mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite Mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1 the Mitochondrion is retracted away from the pellicle and instead is collapsed, as only normally seen in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth and proper mitochondrial morphology is a prerequisite for mitochondrial division. IMPORTANCE Toxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and the congenitally infected. Current therapies are not effective against all life stages of the parasite and many cause toxic effects. The single Mitochondrion of this parasite is a validated drug target and it changes its shape throughout its life cycle. When the parasite is inside of a cell, the Mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood nor are the proteins involved currently known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.
Kenneth Stuart - One of the best experts on this subject based on the ideXlab platform.
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a comprehensive analysis of trypanosoma brucei mitochondrial proteome
Proteomics, 2009Co-Authors: Aswini K Panigrahi, Yuko Ogata, Alena Zikova, Atashi Anupama, Rachel A Dalley, Nathalie Acestor, Peter J Myler, Kenneth StuartAbstract:The composition of the large, single, Mitochondrion of T. brucei was characterized by mass spectrometry (2D-LC-MS/MS and gel-LC-MS/MS) analyses. A total of 2,897 proteins representing a substantial proportion of procyclic form cellular proteome were identified, which confirmed the validity of the vast majority of gene predictions. The data also showed that the genes annotated as hypothetical (species specific) were over-predicted and that virtually all genes annotated as hypothetical, unlikely are not expressed. By comparing the mass spectrometry data with genome sequence, 40 genes were identified that were not previously predicted. The data are placed in a publicly available web-based database (www.TrypsProteome.org). The total mitochondrial proteome is estimated at 1,008 proteins, with 401, 196, and 283 assigned to the Mitochondrion with high, moderate, and lower confidence, respectively. The remaining mitochondrial proteins were estimated by statistical methods although individual assignments could not be made. The identified proteins have predicted roles in macromolecular, metabolic, energy generating, and transport processes providing a comprehensive profile of the protein content and function of the T. brucei Mitochondrion.
Robert A. Charvat - One of the best experts on this subject based on the ideXlab platform.
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identification of fis1 interactors in toxoplasma gondii reveals a novel protein required for peripheral distribution of the Mitochondrion
Mbio, 2020Co-Authors: Kylie Jacobs, Robert A. Charvat, Gustavo ArrizabalagaAbstract:ABSTRACT Toxoplasma gondii’s single Mitochondrion is very dynamic and undergoes morphological changes throughout the parasite’s life cycle. During parasite division, the Mitochondrion elongates, enters the daughter cells just prior to cytokinesis, and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular environment to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane and that this effect depends on the function of the fission-related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant-negative effect that affects the morphology of the Mitochondrion. As this suggests that Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner, we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the Mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite Mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1, the Mitochondrion is retracted away from the pellicle and instead is collapsed, as normally seen only in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth, and proper mitochondrial morphology is a prerequisite for mitochondrial division. IMPORTANCEToxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and congenitally infected. Current therapies are not effective against all life stages of the parasite, and many cause toxic effects. The single Mitochondrion of this parasite is a validated drug target, and it changes its shape throughout its life cycle. When the parasite is inside a cell, the Mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood and the proteins involved are currently not known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.
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Identification of Fis1 interactors in Toxoplasma gondii reveals a novel protein required for peripheral distribution of the Mitochondrion
bioRxiv, 2019Co-Authors: Kylie Jacobs, Robert A. Charvat, Gustavo ArrizabalagaAbstract:ABSTRACT Toxoplasma gondii’s singular Mitochondrion is very dynamic and undergoes morphological changes throughout the parasite’s life cycle. During parasite division, the Mitochondrion elongates, enters the daughter cells just prior to cytokinesis and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane, and that this effect depends on the function of the fission related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant negative effect that affects the morphology of the Mitochondrion. As this suggests Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the Mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite Mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1 the Mitochondrion is retracted away from the pellicle and instead is collapsed, as only normally seen in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth and proper mitochondrial morphology is a prerequisite for mitochondrial division. IMPORTANCE Toxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and the congenitally infected. Current therapies are not effective against all life stages of the parasite and many cause toxic effects. The single Mitochondrion of this parasite is a validated drug target and it changes its shape throughout its life cycle. When the parasite is inside of a cell, the Mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood nor are the proteins involved currently known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.
Jeffrey D. Palmer - One of the best experts on this subject based on the ideXlab platform.
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RNA-mediated transfer of the gene coxll from the Mitochondrion to the nucleus during flowering plant evolution
Trends in Cell Biology, 1991Co-Authors: Jacqueline M. Nugent, Jeffrey D. PalmerAbstract:The gene coxII, normally present in the Mitochondrion, was functionally transferred to the nucleus during flowering plant evolution. coxII transfer is estimated to have occurred between 60 and 200 million years ago, whereas loss of coxII from the Mitochondrion occurred much more recently, being restricted to a single genus of legumes. Most legumes have coxII in both the nucleus and the Mitochondrion; however, no evidence is found for simultaneous coxII expression in both compartments. The nuclear coxII sequence more closely resembles edited mitochondrial coxII transcripts than the genes encoding these RNAs. Hence, gene transfer appears to have involved reverse transcription of an edited RNA intermediate. The nuclear gene contains an intron at the junction of the transit peptide sequence and the mature protein-coding sequence; exon shuffling may have played a role in assembling a functional coxII gene in the nucleus.
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RNA-mediated transfer of the gene coxII from the Mitochondrion to the nucleus during flowering plant evolution
Cell, 1991Co-Authors: Jacqueline M. Nugent, Jeffrey D. PalmerAbstract:Abstract The gene coxII , normally present in the Mitochondrion, was functionally transferred to the nucleus during flowering plant evolution. coxII transfer is estimated to have occurred between 60 and 200 million years ago, whereas loss of coxII from the Mitochondrion occurred much more recently, being restricted to a single genus of legumes. Most legumes have coxII in both the nucleus and the Mitochondrion; however, no evidence is found for simultaneous coxII expression in both compartments. The nuclear coxII sequence more closely resembles edited mitochondrial coxII transcripts than the genes encoding these RNAs. Hence, gene transfer appears to have involved reverse transcription of an edited RNA intermediate. The nuclear gene contains an intron at the junction of the transit peptide sequence and the mature protein-coding sequence; exon shuffling may have played a role in assembling a functional coxII gene in the nucleus.