PMID- 29540758 OWN - NLM STAT- MEDLINE DCOM- 20190910 LR - 20190910 IS - 1748-7838 (Electronic) IS - 1001-0602 (Print) IS - 1001-0602 (Linking) VI - 28 IP - 4 DP - 2018 Apr TI - Malate transported from chloroplast to mitochondrion triggers production of ROS and PCD in Arabidopsis thaliana. PG - 448-461 LID - 10.1038/s41422-018-0024-8 [doi] AB - Programmed cell death (PCD) is a fundamental biological process. Deficiency in MOSAIC DEATH 1 (MOD1), a plastid-localized enoyl-ACP reductase, leads to the accumulation of reactive oxygen species (ROS) and PCD, which can be suppressed by mitochondrial complex I mutations, indicating a signal from chloroplasts to mitochondria. However, this signal remains to be elucidated. In this study, through cloning and analyzing a series of mod1 suppressors, we reveal a comprehensive organelle communication pathway that regulates the generation of mitochondrial ROS and triggers PCD. We show that mutations in PLASTIDIAL NAD-DEPENDENT MALATE DEHYDROGENASE (plNAD-MDH), chloroplastic DICARBOXYLATE TRANSPORTER 1 (DiT1) and MITOCHONDRIAL MALATE DEHYDROGENASE 1 (mMDH1) can each rescue the ROS accumulation and PCD phenotypes in mod1, demonstrating a direct communication from chloroplasts to mitochondria via the malate shuttle. Further studies demonstrate that these elements play critical roles in the redox homeostasis and plant growth under different photoperiod conditions. Moreover, we reveal that the ROS level and PCD are significantly increased in malate-treated HeLa cells, which can be dramatically attenuated by knockdown of the human gene MDH2, an ortholog of Arabidopsis mMDH1. These results uncover a conserved malate-induced PCD pathway in plant and animal systems, revolutionizing our understanding of the communication between organelles. FAU - Zhao, Yannan AU - Zhao Y AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Luo, Lilan AU - Luo L AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. FAU - Xu, Jiesi AU - Xu J AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. FAU - Xin, Peiyong AU - Xin P AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. FAU - Guo, Hongyan AU - Guo H AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. FAU - Wu, Jian AU - Wu J AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Department of Plant Science, Weizmann Institute of Science, Rehovot, 7610001, Israel. FAU - Bai, Lin AU - Bai L AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Wang, Guodong AU - Wang G AUID- ORCID: 0000-0001-9917-0656 AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. FAU - Chu, Jinfang AU - Chu J AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. FAU - Zuo, Jianru AU - Zuo J AUID- ORCID: 0000-0002-9605-3822 AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Yu, Hong AU - Yu H AUID- ORCID: 0000-0002-1748-8693 AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. hyu@genetics.ac.cn. FAU - Huang, Xun AU - Huang X AD - University of Chinese Academy of Sciences, Beijing, 100049, China. xhuang@genetics.ac.cn. AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. xhuang@genetics.ac.cn. FAU - Li, Jiayang AU - Li J AUID- ORCID: 0000-0002-0487-6574 AD - State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. jyli@genetics.ac.cn. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. jyli@genetics.ac.cn. LA - eng PT - Journal Article DEP - 20180314 PL - England TA - Cell Res JT - Cell research JID - 9425763 RN - 0 (Arabidopsis Proteins) RN - 0 (Malates) RN - 0 (Reactive Oxygen Species) RN - 817L1N4CKP (malic acid) RN - EC 1.1.1.37 (Malate Dehydrogenase) SB - IM CIN - Cell Res. 2018 Jun;28(6):609-610. PMID: 29844581 MH - Apoptosis MH - Arabidopsis/*cytology/*metabolism MH - Arabidopsis Proteins/metabolism MH - Biological Transport MH - Cell Death MH - Chloroplasts/*metabolism MH - Malate Dehydrogenase/metabolism MH - Malates/*metabolism MH - Mitochondria/*metabolism MH - Reactive Oxygen Species/*metabolism PMC - PMC5939044 COIS- The authors declare no competing interests. EDAT- 2018/03/16 06:00 MHDA- 2019/09/11 06:00 PMCR- 2019/04/01 CRDT- 2018/03/16 06:00 PHST- 2017/12/25 00:00 [received] PHST- 2018/02/13 00:00 [accepted] PHST- 2018/02/11 00:00 [revised] PHST- 2018/03/16 06:00 [pubmed] PHST- 2019/09/11 06:00 [medline] PHST- 2018/03/16 06:00 [entrez] PHST- 2019/04/01 00:00 [pmc-release] AID - 10.1038/s41422-018-0024-8 [pii] AID - 24 [pii] AID - 10.1038/s41422-018-0024-8 [doi] PST - ppublish SO - Cell Res. 2018 Apr;28(4):448-461. doi: 10.1038/s41422-018-0024-8. Epub 2018 Mar 14.