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Phosphorylation-Induced Motor Shedding Is Required at Mitosis for Proper Distribution and Passive Inheritance of
Jarom Yan-Ming Chung1, Judith Arunodhaya Steen2, Thomas Lewis Schwarz1
1The 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.
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.
Insights
During mitosis, mitochondria detach from spindle microtubules because motor proteins are shed from their surface. This regulated release ensures proper mitochondrial distribution to daughter cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Mitochondrial Dynamics
Background:
- Mitochondria associate with microtubules during interphase.
- Mitotic mitochondria redistribute to the cell periphery, dissociating from spindle microtubules.
Purpose of the Study:
- To elucidate the mechanism behind mitotic mitochondrial redistribution.
- To investigate the role of motor proteins in mitochondrial positioning during mitosis.
Main Methods:
- Investigated mitochondrial redistribution mechanisms.
- Analyzed the role of kinesin and dynein in mitochondrial-microtubule interactions.
- Examined the impact of motor protein shedding on mitochondrial inheritance and cell cycle progression.
Main Results:
- Mitochondrial redistribution is not due to active transport or cytoskeleton tethering.
- Kinesin and dynein motors are shed from the mitochondrial surface during mitosis.
- Phosphorylation by CDK1 and Aurora A drives motor protein shedding.
- Forced motor protein binding disrupts mitochondrial distribution and inheritance.
- Mitochondria with bound dynein can arrest the cell cycle and cause binucleation.
Conclusions:
- Regulated release of motor proteins from mitochondria is crucial for proper cell division.
- This shedding mechanism ensures balanced mitochondrial inheritance.
- Disruption of this process leads to cell cycle arrest and abnormal cell formation.
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