PMID- 29769325 OWN - NLM STAT- MEDLINE DCOM- 20190313 LR - 20191210 IS - 1532-2548 (Electronic) IS - 0032-0889 (Print) IS - 0032-0889 (Linking) VI - 177 IP - 3 DP - 2018 Jul TI - The Ancient Phosphatidylinositol 3-Kinase Signaling System Is a Master Regulator of Energy and Carbon Metabolism in Algae. PG - 1050-1065 LID - 10.1104/pp.17.01780 [doi] AB - Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy and hyper-accumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and "omics" approaches to demonstrate that PI3K signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents. Lipid profiling of wild-type and PI3K KD lines showed significantly reduced membrane lipid breakdown under nitrogen starvation (-N) in the KD. RNA-seq and network analyses showed that under -N conditions, the KD line carried out lipogenesis rather than lipid hydrolysis by initiating de novo fatty acid biosynthesis, which was supported by tricarboxylic acid cycle down-regulation and via acetyl-CoA synthesis from glycolysis. Remarkably, autophagic responses did not have primacy over inositide signaling in algae, unlike in mammals and vascular plants. The mutant displayed a fundamental shift in intracellular energy flux, analogous to that in tumor cells. The high free fatty acid levels and reduced mitochondrial ATP generation led to decreased cell viability. These results indicate that the PI3K signal transduction pathway is the metabolic gatekeeper restraining biofuel yields, thus maintaining fitness and viability under stress in algae. This study demonstrates the existence of homeostasis between starch and lipid synthesis controlled by lipid signaling in algae and expands our understanding of such processes, with biotechnological and evolutionary implications. CI - (c) 2018 American Society of Plant Biologists. All rights reserved. FAU - Ramanan, Rishiram AU - Ramanan R AUID- ORCID: 0000-0002-4641-9603 AD - Department of Environmental Science, School of Earth Science Systems, Central University of Kerala, Tejaswini Hills, Periya, Kasaragod 671316, Kerala, India. AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Tran, Quynh-Giao AU - Tran QG AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. AD - Department of Environmental Biotechnology, KRIBB School of Biotechnology, Korea University of Science and Technology, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Cho, Dae-Hyun AU - Cho DH AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Jung, Jae-Eun AU - Jung JE AUID- ORCID: 0000-0001-5179-4603 AD - Genome Research Center, KRIBB, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Kim, Byung-Hyuk AU - Kim BH AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Shin, Sang-Yoon AU - Shin SY AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. AD - Department of Environmental Biotechnology, KRIBB School of Biotechnology, Korea University of Science and Technology, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Choi, Sae-Hae AU - Choi SH AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Liu, Kwang-Hyeon AU - Liu KH AUID- ORCID: 0000-0002-3285-5594 AD - College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea. FAU - Kim, Dae-Soo AU - Kim DS AD - Genome Research Center, KRIBB, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Lee, Seon-Jin AU - Lee SJ AD - Biomedical Genomics Research Center, KRIBB, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Crespo, Jose L AU - Crespo JL AUID- ORCID: 0000-0003-3514-1025 AD - Instituto de Bioquimica Vegetal y Fotosintesis, Consejo Superior de Investigaciones Cientificas, Universidad de Sevilla, Seville 41092, Spain. FAU - Lee, Hee-Gu AU - Lee HG AD - Biomedical Genomics Research Center, KRIBB, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Oh, Hee-Mock AU - Oh HM AUID- ORCID: 0000-0002-2151-3687 AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea. AD - Department of Environmental Biotechnology, KRIBB School of Biotechnology, Korea University of Science and Technology, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Kim, Hee-Sik AU - Kim HS AUID- ORCID: 0000-0002-9500-5394 AD - Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea hkim@kribb.re.kr. AD - Department of Environmental Biotechnology, KRIBB School of Biotechnology, Korea University of Science and Technology, Yuseong-gu, Daejeon 34141, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180516 PL - United States TA - Plant Physiol JT - Plant physiology JID - 0401224 RN - 0 (Enzyme Inhibitors) RN - 0 (Membrane Lipids) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Plant Proteins) RN - 7440-44-0 (Carbon) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 9005-25-8 (Starch) SB - IM MH - Adenosine Triphosphate/metabolism MH - Autophagy/physiology MH - Carbon/*metabolism MH - Chlamydomonas reinhardtii/drug effects/genetics/*metabolism MH - Energy Metabolism/*physiology MH - Enzyme Inhibitors/pharmacology MH - Gene Knockdown Techniques MH - Lipid Metabolism/genetics MH - Membrane Lipids/genetics/metabolism MH - Mutation MH - Phosphatidylinositol 3-Kinases/genetics/*metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phylogeny MH - Plant Proteins/genetics/*metabolism MH - Scenedesmus/drug effects/metabolism MH - Signal Transduction MH - Starch/genetics/metabolism PMC - PMC6053016 EDAT- 2018/05/18 06:00 MHDA- 2019/03/14 06:00 PMCR- 2018/05/16 CRDT- 2018/05/18 06:00 PHST- 2018/03/22 00:00 [received] PHST- 2018/05/02 00:00 [accepted] PHST- 2018/05/18 06:00 [pubmed] PHST- 2019/03/14 06:00 [medline] PHST- 2018/05/18 06:00 [entrez] PHST- 2018/05/16 00:00 [pmc-release] AID - pp.17.01780 [pii] AID - 201701780DR1 [pii] AID - 10.1104/pp.17.01780 [doi] PST - ppublish SO - Plant Physiol. 2018 Jul;177(3):1050-1065. doi: 10.1104/pp.17.01780. Epub 2018 May 16.