Developmentally regulated GTP-binding protein 2 depletion leads to mitochondrial dysfunction through downregulation of dynamin-related protein 1
Autor: | Wha Ja Cho, Kyungjin Kim, Eun Hye Yoon, Byung Ju Lee, Jeong Woo Park, Chang Man Ha, Unn Hwa Lee, Myoung Seok Ko, Mai-Tram Vo |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Dynamins endocrine system Biophysics Down-Regulation Biology Biochemistry Mitochondrial apoptosis-induced channel Mitochondrial Dynamics GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences DNM1L GTP-Binding Proteins Humans Molecular Biology Cell Biology Molecular biology Cell biology Mitochondria 030104 developmental biology mitochondrial fusion Mitochondrial permeability transition pore DNAJA3 Apoptosis-inducing factor Mitochondrial fission ATP–ADP translocase Microtubule-Associated Proteins HeLa Cells |
Zdroj: | Biochemical and biophysical research communications. 486(4) |
ISSN: | 1090-2104 |
Popis: | 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. |
Databáze: | OpenAIRE |
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