Dysfunction of PLK1/Cyclin B1/Cdk1/Drp1 axis leading to Multipolar Spindle Formation-From Mitochondria to Centrosome

• Main Authors: Bo-Xiu Hsiao, 蕭博修
• Other Authors: Yi-Ren Hong
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/b986sj

碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 105 === Background: Mitochondria are a double membrane-bound organelle that produces ATP through electron transfer and oxidative phosphorylation, which is a tubule-vesicular reticulum shape and maintain its structure by dynamic fission and fusion events. Blockade of mitochondrial electron transport chain (ETC) has been recently shown to cause overduplicated centrosomes leading to chromosome misalignment and chromosomal instability (CIN). Moreover, mitochondrial hyperfusion directly inducing genome instability by replication stress has been demonstrated. Although several studies have reported that mitochondria are implicated in centrosome function, the communication between organelles remains elusive. Methods: We firstly examined the related proteins between centrosome and mitochondria under the treatment of mitochondrial ETC inhibitors. Confocal microscopy was used to observe the morphology of the mitotic spindle in mitosis after cells with mitochondrial ETC inhibitors treatment and being synchronized at M phase. Results: The abnormal mitotic formation in HeLa cells was demonstrated by inhibition of mitochondrial ETC in confocal microscopy. PLK1 T210 was decreased under the treatment of antimycin A (AA) but not rotenone (ROT). The downstream proteins of PLK1 were also decreased under the AA treatment. Mitochondrial hyperfusion induced by decreasing of the fission protein Drp1 S616 through Cyclin B1/Cdk1 was regulated by PLK1 in the presence of AA rather than ROT. Thus, these data suggest the role of mitochondrial ETC in maintaining numeral centrosomal homeostasis that evades multipolarity. Discussion: Altogether, we established a model to illustrate that PLK1 regulates the function of Drp1 through Cyclin B1/Cdk1 and as well as being affected by mitochondrial ETC inhibitor treatment in cell cycle progression. Downregulation of PLK1 in HeLa cells by mitochondrial ETC inhibitor treatment underscores the importance of centrosome and mitochondria crosstalk and may underlie the observed mitotic aberrations.