Phosphorylation-Induced Motor Shedding Is Required at Mitosis for Proper Distribution and Passive Inheritance of Mitochondria

• Mitochondria distribute passively during mitosis upon their release from microtubules
• Mitochondrial shedding of motors releases mitochondria from microtubules
• Forced motor attachment leads to asymmetric mitochondrial inheritance
• Mitochondrial attachment to the spindle causes mitotic arrest and multinucleate cells

SummaryWhile 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.

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