title: Megakaryocytic differentiation of K562 cells induced by PMA reduced the activity of respiratory chain complex IV.
abstract: Mitochondria are involved in the regulation of cell differentiation processes, but its function changes and molecular mechanisms are not yet clear. In this study, we found that mitochondrial functions changed obviously when K562 cells were induced to megakaryocytic differentiation by phorbol 12-myristate 13-acetate (PMA). During the cell differentiation, the reactive oxygen species (ROS) level was increased, mitochondrial membrane potential declined and respiratory chain complex IV activity was decreased. Treatment with specific inhibitor of mitochondrial respiratory chain complex IV led to a significant inhibition in mitochondrial membrane potential and reduction of PMA-induced cell differentiation. However, treatment with cyclosporine A, a stabilization reagent of mitochondrial membrane potential, did not improve the down-regulation of mitochondrial respiratory chain complex IV induced by PMA. Furthermore, we found that the level of the complex IV core subunit COX3 and mitochondrial transport-related proteins Tim9 and Tim10 were decreased during the differentiation of K562 cells induced by PMA, suggesting an important role of these factors in mitochondrial functional changes. Our results suggest that changes in mitochondrial functions are involved in the PMA-induced K562 cell differentiation process, and the maintenance of the steady-state of mitochondrial functions plays a critical role in the regulation of cell differentiation.
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Yin
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Zhan
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Chang-hui
authors.initials: CH
authors.lastname: Ge
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D013755:Tetradecanoylphorbol Acetate