title: Developmentally regulated GTP-binding protein 2 depletion leads to mitochondrial dysfunction through downregulation of dynamin-related protein 1.
abstract: Mitochondrial dynamics, including constant fusion and fission, play critical roles in maintaining mitochondrial morphology and function. Here, we report that developmentally regulated GTP-binding protein 2 (DRG2) regulates mitochondrial morphology by modulating the expression of the mitochondrial fission gene dynamin-related protein 1 (Drp1). shRNA-mediated silencing of DRG2 induced mitochondrial swelling, whereas expression of an shRNA-resistant version of DRG2 decreased mitochondrial swelling in DRG2-depleted cells. Analysis of the expression levels of genes involved in mitochondrial fusion and fission revealed that DRG2 depletion significantly decreased the level of Drp1. Overexpression of Drp1 rescued the defect in mitochondrial morphology induced by DRG2 depletion. DRG2 depletion reduced the mitochondrial membrane potential, oxygen consumption rate (OCR), and amount of mitochondrial DNA (mtDNA), whereas it increased reactive oxygen species (ROS) production and apoptosis. Taken together, our data demonstrate that DRG2 acts as a regulator of mitochondrial fission by controlling the expression of Drp1.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
authors.forename: Mai-Tram
authors.initials: MT
authors.lastname: Vo
authors.affiliation: Asan Medical Center, 88 Olympic-ro 43-Gil, Songpa-gu, Seoul 05505, South Korea.
authors.forename: Myoung Seok
authors.initials: MS
authors.lastname: Ko
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
authors.forename: Unn Hwa
authors.initials: UH
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Yoon
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: Research Division, Korea Brain Research Institute, Daegu 41068, South Korea.
authors.forename: Chang Man
authors.initials: CM
authors.lastname: Ha
authors.affiliation: Research Division, Korea Brain Research Institute, Daegu 41068, South Korea; Department of Brain and Cognitive Science, DGIST, Daegu 711-873, South Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea. Electronic address: jwpark@ulsan.ac.kr.
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D015536:Down-Regulation / Q000502:physiology; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*
chemical_list: C409877:DRG2 protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C110768:DNM1L protein, human; D034281:Dynamins
keywords: DRG2; Drp1; Mitochondrial dysfunction; Mitochondrial swelling