Sirt3 controls chromosome alignment by regulating spindle dynamics during mitosis.
Sirt3, one of mammalian sirtuins is a prominent mitochondrial deacetylase that controls mitochondrial oxidative pathways and the rate of reactive oxygen species. Sirt3 also regulates energy metabolism by deacetylating enzymes involved in the metabolic pathway related with lifespan. We report here a novel function of Sirt3 which was found to be involved in mitosis. Depletion of the Sirt3 protein generated unaligned chromosomes in metaphase which caused mitotic arrest by activating spindle assembly checkpoint (SAC). Furthermore, the shape and the amount of the spindles in Sirt3 depleted cells were abnormal. Microtubule (MT) polymerization also increased in Sirt3 depleted cells, suggesting that Sirt3 is involved in spindle dynamics. However, the level of acetylated tubulin was not increased significantly in Sirt3 depleted cells. The findings collectively suggest that Sirt3 is not a tubulin deacetylase but regulates the attachment of spindle MTs to the kinetochore and the subsequent chromosome alignment by increasing spindle dynamics.
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Byung-Soo
BS
Choi
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Ji Eun
JE
Park
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea. Electronic address: cyjang@sookmyung.ac.kr.
Chang-Young
CY
Jang
D002875:Chromosomes / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure
D034741:RNA, Small Interfering; C466093:SIRT3 protein, human; D056566:Sirtuin 3
Chromosome alignment; Sirt3; Spindle assembly checkpoint; Spindle dynamics