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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.
Highlights
The mitochondria perform three important functions in the cells: energy production, execution and amplification of cell death pathways, and signal pathway regulation
We found that mitochondrial functions altered significantly when K562 cells were induced to megakaryocytic differentiation by phorbol 12-myristate 13-acetate (PMA)
& 6D, sodium azide (SA) treatment significantly decreased the ratio of CD41- and CD61-positive cell in a dose-dependent manner. These results suggested that complex IV involved in megakaryocytic differentiation of K562 cells induced by PMA through regulating mitochondrial membrane potential
Summary
The mitochondria perform three important functions in the cells: energy production, execution and amplification of cell death pathways, and signal pathway regulation. ATP production is a key function of the mitochondria, a large number of accumulated evidences suggested that mitochondria are involved in the regulation of cell differentiation process. The inhibition of mitochondrial protein synthesis affect the differentiation of a variety of cells, including mouse erythroleukemia [6] and mastocytoma cells [7], neurons [8], and human [9], avian [10], or murine myoblasts [11]. The mitochondrial super complex will undergo changes in the differentiation processes of a variety of cells [14]
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