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J. Biol. Chem., Vol. 282, Issue 15, 11521-11529, April 13, 2007

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Mitotic Phosphorylation of Dynamin-related GTPase Drp1 Participates in Mitochondrial Fission^*

From the Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan

Organelles are inherited to daughter cells beyond dynamic changes of the membrane structure during mitosis. Mitochondria are dynamic entities, frequently dividing and fusing with each other, during which dynamin-related GTPase Drp1 is required for the fission reaction. In this study, we analyzed mitochondrial dynamics in mitotic mammalian cells. Although mitochondria in interphase HeLa cells are long tubular network structures, they are fragmented in early mitotic phase, and the filamentous network structures are subsequently reformed in the daughter cells. In marked contrast, tubular mitochondrial structures are maintained during mitosis in Drp1 knockdown cells, indicating that the mitochondrial fragmentation in mitosis requires mitochondrial fission by Drp1. Drp1 was specifically phosphorylated in mitosis by Cdk1/cyclin B on Ser-585. Exogenous expression of unphosphorylated mutant Drp1^S585A led to reduced mitotic mitochondrial fragmentation. These results suggest that phosphorylation of Drp1 on Ser-585 promotes mitochondrial fission in mitotic cells.

Received for publication, August 1, 2006 , and in revised form, January 9, 2007.

^* This work was supported by grants from the Ministry of Education, Science, and Culture of Japan, Core Research from Evolutional Science and Technology, and Takara Science Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1A-C and Movies 1-5.

¹ To whom correspondence should be addressed: Dept. of Molecular Biology, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Tel.: 81-92-642-4709; Fax: 81-92-642-6183; E-mail: mihara{at}cell.med.kyushu-u.ac.jp.

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