title: Phosphorylation-Induced Motor Shedding Is Required at Mitosis for Proper Distribution and Passive Inheritance of Mitochondria.
abstract: While interphase mitochondria associate with microtubules, mitotic mitochondria dissociate from spindle microtubules and localize in the cell periphery. Here, we show that this redistribution is not mediated by mitochondrial active transport or tethering to the cytoskeleton. Instead, kinesin and dynein, which link mitochondria to microtubules, are shed from the mitochondrial surface. Shedding is driven by phosphorylation of mitochondrial and cytoplasmic targets by CDK1 and Aurora A. Forced recruitment of motor proteins to mitotic mitochondria to override this shedding prevents their proper symmetrical distribution and disrupts the balanced inheritance of mitochondria to daughter cells. Moreover, when mitochondria with bound dynein bind to the mitotic spindle, they arrest cell-cycle progression and produce binucleate cells. Thus, our results show that the regulated release of motor proteins from the mitochondrial surface is a critical mitotic event.
authors.affiliation: The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston MA 02115, USA.
authors.forename: Jarom Yan-Ming
authors.initials: JY
authors.lastname: Chung
authors.affiliation: The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston MA 02115, USA.
authors.forename: Judith Arunodhaya
authors.initials: JA
authors.lastname: Steen
authors.affiliation: The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston MA 02115, USA. Electronic address: thomas.schwarz@childrens.harvard.edu.
authors.forename: Thomas Lewis
authors.initials: TL
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004398:Dyneins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis; D010766:Phosphorylation; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C576917:AURKA protein, human; D064096:Aurora Kinase A; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D004398:Dyneins; D016547:Kinesins