The algal past and parasite present of the apicoplast.

Plasmodium and Toxoplasma are genera of apicomplexan parasites that infect millions of people each year. The former causes malaria, and the latter causes neurotropic infections associated with a weakened or developing immune system. These parasites harbor a peculiar organelle, the apicoplast. The apicoplast is the product of an ancient endosymbiosis between a heterotrophic and a photosynthetic protist. We explore the cellular and molecular mechanisms that enabled a stable union of two previously independent organisms. These include the exchange of metabolites, transfer of genes, transport of proteins, and overall coordination of biogenesis and proliferation. These mechanisms are still active today and can be exploited to treat parasite infection. They were shaped by the dramatic changes that occurred in the evolution of the phylum Apicomplexa--including the gain and loss of photosynthesis, adaptation to symbiosis and parasitism, and the explosion of animal diversity-that ultimately provided an aquatic alga access to every biotope on this planet.

[1]  G. Schneider,et al.  An Unusual ERAD-Like Complex Is Targeted to the Apicoplast of Plasmodium falciparum , 2009, Eukaryotic Cell.

[2]  Joseph L. DeRisi,et al.  Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum , 2011, PLoS biology.

[3]  I. Coppens,et al.  A Membrane Protease is Targeted to the Relict Plastid of Toxoplasma via an Internal Signal Sequence , 2007, Traffic.

[4]  N. Chua,et al.  In vitro synthesis and processing of a putative precursor for the small subunit of ribulose-1,5-bisphosphate carboxylase of Chlamydomonas reinhardtii. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Ansgar Gruber,et al.  Der1-mediated preprotein import into the periplastid compartment of chromalveolates? , 2007, Molecular biology and evolution.

[6]  Swati Agrawal,et al.  Toxoplasma gondii Tic20 is essential for apicoplast protein import , 2008, Proceedings of the National Academy of Sciences.

[7]  S. Miyagishima,et al.  Identification of cyanobacterial cell division genes by comparative and mutational analyses , 2005, Molecular microbiology.

[8]  G. McFadden,et al.  The carbon and energy sources of the non‐photosynthetic plastid in the malaria parasite , 2010, FEBS letters.

[9]  Peter J. Bradley,et al.  A Thioredoxin Family Protein of the Apicoplast Periphery Identifies Abundant Candidate Transport Vesicles in Toxoplasma gondii , 2008, Eukaryotic Cell.

[10]  J. Soll,et al.  Tic20 forms a channel independent of Tic110 in chloroplasts , 2011, BMC Plant Biology.

[11]  H. Vial,et al.  Phosphatidylinositol 3-Phosphate, an Essential Lipid in Plasmodium, Localizes to the Food Vacuole Membrane and the Apicoplast , 2010, Eukaryotic Cell.

[12]  G. McFadden,et al.  Tic22 Is an Essential Chaperone Required for Protein Import into the Apicoplast* , 2012, The Journal of Biological Chemistry.

[13]  H. Lichtenthaler,et al.  Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. , 1999, Science.

[14]  A. Weber,et al.  Single, Ancient Origin of a Plastid Metabolite Translocator Family in Plantae from an Endomembrane-Derived Ancestor , 2006, Eukaryotic Cell.

[15]  K. L. Le Roch,et al.  An Apicoplast Localized Ubiquitylation System Is Required for the Import of Nuclear-encoded Plastid Proteins , 2013, PLoS pathogens.

[16]  I. Gluzman,et al.  A role for falcilysin in transit peptide degradation in the Plasmodium falciparum apicoplast , 2007, Molecular microbiology.

[17]  Kami Kim,et al.  Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle , 2011, Proceedings of the National Academy of Sciences.

[18]  Joel S. Freundlich,et al.  The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites. , 2008, Cell host & microbe.

[19]  Michael S. Behnke,et al.  A Systematic Screen to Discover and Analyze Apicoplast Proteins Identifies a Conserved and Essential Protein Import Factor , 2011, PLoS pathogens.

[20]  B. Striepen,et al.  Cell Division in Apicomplexan Parasites Is Organized by a Homolog of the Striated Rootlet Fiber of Algal Flagella , 2012, PLoS biology.

[21]  B. Humbel,et al.  A Novel Dynamin-Related Protein Has Been Recruited for Apicoplast Fission in Toxoplasma gondii , 2009, Current Biology.

[22]  A. Vaughan,et al.  Type II fatty acid synthesis is essential only for malaria parasite late liver stage development , 2008, Cellular microbiology.

[23]  G. V. van Dooren,et al.  Building the Perfect Parasite: Cell Division in Apicomplexa , 2007, PLoS pathogens.

[24]  J. Saldanha,et al.  Nifs and Sufs in malaria , 2001, Molecular microbiology.

[25]  M. Parsons,et al.  Analysis of targeting sequences demonstrates that trafficking to the Toxoplasma gondii plastid branches off the secretory system. , 2000, Journal of cell science.

[26]  K. M. Watts,et al.  A second target of the antimalarial and antibacterial agent fosmidomycin revealed by cellular metabolic profiling. , 2011, Biochemistry.

[27]  R. Wilson,et al.  Targeting GFP to the malarial mitochondrion. , 2003, Molecular and biochemical parasitology.

[28]  B. Striepen,et al.  Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii , 2006, Proceedings of the National Academy of Sciences.

[29]  P. Keeling Chromalveolates and the Evolution of Plastids by Secondary Endosymbiosis 1 , 2009, The Journal of eukaryotic microbiology.

[30]  J. Froehlich,et al.  ARC5, a cytosolic dynamin-like protein from plants, is part of the chloroplast division machinery , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[31]  S. Theg,et al.  The chloroplast protein import system: from algae to trees. , 2013, Biochimica et biophysica acta.

[32]  U. Maier,et al.  ERAD-derived preprotein transport across the second outermost plastid membrane of diatoms. , 2009, Molecular biology and evolution.

[33]  G. McFadden,et al.  Metabolic maps and functions of the Plasmodium mitochondrion. , 2006, FEMS microbiology reviews.

[34]  G. McFadden,et al.  Evolution: Red Algal Genome Affirms a Common Origin of All Plastids , 2004, Current Biology.

[35]  D. Roos,et al.  Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Dong Wook Lee,et al.  A 1-Megadalton Translocation Complex Containing Tic20 and Tic21 Mediates Chloroplast Protein Import at the Inner Envelope Membrane[W] , 2009, The Plant Cell Online.

[37]  Christopher J. Tonkin,et al.  Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum , 2005, Molecular microbiology.

[38]  Enrico Schleiff,et al.  A GTP-driven motor moves proteins across the outer envelope of chloroplasts , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[39]  H. Vial,et al.  Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis , 2011, PLoS pathogens.

[40]  Jeff Errington,et al.  Bacterial cell division: assembly, maintenance and disassembly of the Z ring , 2009, Nature Reviews Microbiology.

[41]  B. Humbel,et al.  Membrane Contact Sites between Apicoplast and ER in Toxoplasma gondii Revealed by Electron Tomography , 2009, Traffic.

[42]  A. Weber,et al.  Solute transporters of the plastid envelope membrane. , 2005, Annual review of plant biology.

[43]  Christopher J. Tonkin,et al.  Characterization of Two Putative Protein Translocation Components in the Apicoplast of Plasmodium falciparum , 2009, Eukaryotic Cell.

[44]  I. Tews,et al.  Structure and Conservation of the Periplasmic Targeting Factor Tic22 Protein from Plants and Cyanobacteria* , 2012, The Journal of Biological Chemistry.

[45]  M. Parsons,et al.  Apicoplast Targeting of a Toxoplasma gondii Transmembrane Protein Requires a Cytosolic Tyrosine‐Based Motif , 2012, Traffic.

[46]  A. Kastaniotis,et al.  Apicoplast and Endoplasmic Reticulum Cooperate in Fatty Acid Biosynthesis in Apicomplexan Parasite Toxoplasma gondii* , 2011, The Journal of Biological Chemistry.

[47]  Yunde Zhao,et al.  An Allelic Mutant Series of ATM3 Reveals Its Key Role in the Biogenesis of Cytosolic Iron-Sulfur Proteins in Arabidopsis1[C][W][OA] , 2009, Plant Physiology.

[48]  D. Hodge,et al.  Isoprenoid Biosynthesis Inhibition Disrupts Rab5 Localization and Food Vacuolar Integrity in Plasmodium falciparum , 2012, Eukaryotic Cell.

[49]  A. Weber,et al.  The Metabolite Transporters of the Plastid Envelope: An Update , 2011, Front. Plant Sci..

[50]  K. Osteryoung,et al.  Chloroplast Division in Higher Plants Requires Members of Two Functionally Divergent Gene Families with Homology to Bacterial ftsZ , 1998, Plant Cell.

[51]  U. Maier,et al.  Distribution of the SELMA Translocon in Secondary Plastids of Red Algal Origin and Predicted Uncoupling of Ubiquitin-Dependent Translocation from Degradation , 2012, Eukaryotic Cell.

[52]  Karsten Fischer,et al.  The toxoplasma apicoplast phosphate translocator links cytosolic and apicoplast metabolism and is essential for parasite survival. , 2010, Cell host & microbe.

[53]  Christopher J. Tonkin,et al.  Tropical infectious diseases: Metabolic maps and functions of the Plasmodium falciparum apicoplast , 2004, Nature Reviews Microbiology.

[54]  P. Watkins Very-long-chain Acyl-CoA Synthetases* , 2008, Journal of Biological Chemistry.

[55]  G. McFadden,et al.  Processing of an Apicoplast Leader Sequence inPlasmodium falciparum and the Identification of a Putative Leader Cleavage Enzyme* , 2002, The Journal of Biological Chemistry.

[56]  U. Maier,et al.  Filling the Gap, Evolutionarily Conserved Omp85 in Plastids of Chromalveolates* , 2009, The Journal of Biological Chemistry.

[57]  M. Parsons,et al.  Dissection of brefeldin A-sensitive and -insensitive steps in apicoplast protein targeting , 2005, Journal of Cell Science.

[58]  M. Strath,et al.  Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum. , 1996, Journal of molecular biology.

[59]  N. Surolia,et al.  Apicoplast triose phosphate transporter (TPT) gene knockout is lethal for Plasmodium. , 2012, Molecular and biochemical parasitology.

[60]  U. Flügge,et al.  Transport of isoprenoid intermediates across chloroplast envelope membranes. , 2005, Plant biology.

[61]  S. Bhushan,et al.  Characterization of a novel zinc metalloprotease involved in degrading targeting peptides in mitochondria and chloroplasts. , 2003, The Plant journal : for cell and molecular biology.

[62]  B. M. Lange,et al.  Metabolic cross talk between cytosolic and plastidial pathways of isoprenoid biosynthesis: unidirectional transport of intermediates across the chloroplast envelope membrane. , 2003, Archives of biochemistry and biophysics.

[63]  R. Lill,et al.  The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins , 1999, The EMBO journal.

[64]  Harvey T. McMahon,et al.  The dynamin superfamily: universal membrane tubulation and fission molecules? , 2004, Nature Reviews Molecular Cell Biology.

[65]  A. Salih,et al.  Chromera velia is endosymbiotic in larvae of the reef corals Acropora digitifera and A. tenuis. , 2013, Protist.

[66]  A. Weber,et al.  Host origin of plastid solute transporters in the first photosynthetic eukaryotes , 2007, Genome Biology.

[67]  M. Siddiqi,et al.  Interaction between sulphur mobilisation proteins SufB and SufC: evidence for an iron-sulphur cluster biogenesis pathway in the apicoplast of Plasmodium falciparum. , 2011, International journal for parasitology.

[68]  K. Philippar,et al.  Solute channels of the outer membrane: from bacteria to chloroplasts , 2007, Biological chemistry.

[69]  G. McFadden,et al.  The use and abuse of heme in apicomplexan parasites. , 2012, Antioxidants & redox signaling.

[70]  H. Stunnenberg,et al.  Plasmodium falciparum centromeres display a unique epigenetic makeup and cluster prior to and during schizogony , 2012, Cellular microbiology.

[71]  E. Vierling,et al.  Conserved cell and organelle division , 1995, Nature.

[72]  P. Jarvis Targeting of nucleus-encoded proteins to chloroplasts in plants. , 2008, The New phytologist.

[73]  G. McFadden,et al.  Protein trafficking to the plastid of Plasmodium falciparum is via the secretory pathway , 2000, The EMBO journal.

[74]  L. Sibley,et al.  Host cells: mobilizable lipid resources for the intracellular parasite Toxoplasma gondii. , 2002, Journal of cell science.

[75]  B. Striepen,et al.  The cell biology of secondary endosymbiosis – how parasites build, divide and segregate the apicoplast , 2006, Molecular microbiology.

[76]  C. Howe,et al.  What makes a chloroplast? Reconstructing the establishment of photosynthetic symbioses , 2012, Journal of Cell Science.

[77]  B. Striepen,et al.  Plastid segregation and cell division in the apicomplexan parasite Sarcocystis neurona , 2005, Journal of Cell Science.

[78]  I. Coppens,et al.  Cell cycle‐regulated vesicular trafficking of Toxoplasma APT1, a protein localized to multiple apicoplast membranes , 2007, Molecular microbiology.

[79]  Christopher J. Tonkin,et al.  Evidence for Golgi‐independent transport from the early secretory pathway to the plastid in malaria parasites , 2006, Molecular microbiology.

[80]  J. Balk,et al.  Ancient and essential: the assembly of iron-sulfur clusters in plants. , 2011, Trends in plant science.

[81]  S. Ralph,et al.  Membrane transporters in the relict plastid of malaria parasites. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[82]  D. Roos,et al.  The Plastid of Toxoplasma gondii Is Divided by Association with the Centrosomes , 2000, The Journal of cell biology.

[83]  S. Richter,et al.  A chloroplast processing enzyme functions as the general stromal processing peptidase. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[84]  D. Soldati-Favre,et al.  Metabolic pathways in the apicoplast of apicomplexa. , 2010, International review of cell and molecular biology.

[85]  D. Soldati,et al.  Role of Toxoplasma gondii Myosin A in Powering Parasite Gliding and Host Cell Invasion , 2002, Science.

[86]  G. V. van Dooren,et al.  Genetic Evidence that an Endosymbiont-derived Endoplasmic Reticulum-associated Protein Degradation (ERAD) System Functions in Import of Apicoplast Proteins* , 2009, The Journal of Biological Chemistry.

[87]  T. Kuroiwa,et al.  A Plant-Specific Dynamin-Related Protein Forms a Ring at the Chloroplast Division Site Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.009373. , 2003, The Plant Cell Online.

[88]  S. Miyagishima,et al.  Evolutionary linkage between eukaryotic cytokinesis and chloroplast division by dynamin proteins , 2008, Proceedings of the National Academy of Sciences.