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We report that when isoleucine is withdrawn from the culture medium of intraerythrocytic\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    , the parasite slows its metabolism and progresses through its developmental cycle at a reduced rate. Isoleucine-starved parasites remain viable for 72 h and resume rapid growth upon resupplementation. Protein degradation during starvation is important for maintenance of this hibernatory state. Microarray analysis of starved parasites revealed a 60% decrease in the rate of progression through the normal transcriptional program but no other apparent stress response.\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    parasites do not possess a TOR nutrient-sensing pathway and have only a rudimentary amino acid starvation-sensing eukaryotic initiation factor 2\u03b1 (eIF2\u03b1) stress response. Isoleucine deprivation results in GCN2-mediated phosphorylation of eIF2\u03b1, but kinase-knockout clones still are able to hibernate and recover, indicating that this pathway does not directly promote survival during isoleucine starvation. We conclude that\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    , in the absence of canonical eukaryotic nutrient stress-response pathways, can cope with an inconsistent bloodstream amino acid supply by hibernating and waiting for more nutrient to be provided.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1209823109","type":"journal-article","created":{"date-parts":[[2012,10,30]],"date-time":"2012-10-30T01:46:22Z","timestamp":1351561582000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":178,"title":["<i>Plasmodium falciparum<\/i>\n                    responds to amino acid starvation by entering into a hibernatory state"],"prefix":"10.1073","volume":"109","author":[{"given":"Shalon E.","family":"Babbitt","sequence":"first","affiliation":[{"name":"Departments of aMedicine and"},{"name":"Molecular Microbiology and"},{"name":"Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Altenhofen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"},{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Cobbold","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"},{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva S.","family":"Istvan","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"},{"name":"Molecular Microbiology and"},{"name":"Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Fennell","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8TA, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Doerig","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8TA, United Kingdom; and"},{"name":"Department of Microbiology, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Llin\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"},{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"},{"name":"Molecular Microbiology and"},{"name":"Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,10,29]]},"reference":[{"key":"e_1_1_2_18_9_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601876103"},{"key":"e_1_1_2_18_9_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2122003re15"},{"key":"e_1_1_2_18_9_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0340007"},{"key":"e_1_1_2_18_9_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-8-99"},{"key":"e_1_3_4_1_2","first-page":"211","article-title":"Transport of amino acids and nucleic acid precursors in malarial parasites","volume":"55","author":"Sherman IW","year":"1977","unstructured":"IW Sherman, Transport of amino acids and nucleic acid precursors in malarial parasites. 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