title: Death-associated Protein 3 Regulates Mitochondrial-encoded Protein Synthesis and Mitochondrial Dynamics.
abstract: Mitochondrial morphologies change over time and are tightly regulated by dynamic machinery proteins such as dynamin-related protein 1 (Drp1), mitofusion 1/2, and optic atrophy 1 (OPA1). However, the detailed mechanisms of how these molecules cooperate to mediate fission and fusion remain elusive. DAP3 is a mitochondrial ribosomal protein that involves in apoptosis, but its biological function has not been well characterized. Here, we demonstrate that DAP3 specifically localizes in the mitochondrial matrix. Knockdown of DAP3 in mitochondria leads to defects in mitochondrial-encoded protein synthesis and abnormal mitochondrial dynamics. Moreover, depletion of DAP3 dramatically decreases the phosphorylation of Drp1 at Ser-637 on mitochondria, enhancing the retention time of Drp1 puncta on mitochondria during the fission process. Furthermore, autophagy is inhibited in the DAP3-depleted cells, which sensitizes cells to different types of death stimuli. Together, our results suggest that DAP3 plays important roles in mitochondrial function and dynamics, providing new insights into the mechanism of a mitochondrial ribosomal protein function in cell death.
authors: From the Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543.
authors: Lin
authors: L
authors: Xiao
authors: From the Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543.
authors: Hongxu
authors: H
authors: Xian
authors: From the Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543.
authors: Kit Yee
authors: KY
authors: Lee
authors: From the Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543.
authors: Bin
authors: B
authors: Xiao
authors: the Neuroscience and Behavioural Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573.
authors: Hongyan
authors: H
authors: Wang
authors: the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573, the Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, and.
authors: Fengwei
authors: F
authors: Yu
authors: the Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors: Han-Ming
authors: HM
authors: Shen
authors: From the Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543, the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573, dbslyc@nus.edu.sg.
authors: Yih-Cherng
authors: YC
authors: Liou
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D002460:Cell Line; D034281:Dynamins / Q000737:chemistry / Q000378:metabolism; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C097041:DAP3 protein, human; D008565:Membrane Proteins; C533267:Mff protein, human; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D012694:Serine; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: Drp1, DAP3; autophagy; cell death; cell signaling; metabolism; mitochondria