Mitochondria-cytoskeleton associations in mammalian cytokinesis.

C. A. Mandato,E. J. Lawrence,E. Boucher

doi:10.1186/s13008-016-0015-4

Abstract

BackgroundThe role of the cytoskeleton in regulating mitochondrial distribution in dividing mammalian cells is poorly understood. We previously demonstrated that mitochondria are transported to the cleavage furrow during cytokinesis in a microtubule-dependent manner. However, the exact subset of spindle microtubules and molecular machinery involved remains unknown.MethodsWe employed quantitative imaging techniques and structured illumination microscopy to analyse the spatial and temporal relationship of mitochondria with microtubules and actin of the contractile ring during cytokinesis in HeLa cells.ResultsSuperresolution microscopy revealed that mitochondria were associated with astral microtubules of the mitotic spindle in cytokinetic cells. Dominant-negative mutants of KIF5B, the heavy chain of kinesin-1 motor, and of Miro-1 disrupted mitochondrial transport to the furrow. Live imaging revealed that mitochondrial enrichment at the cell equator occurred simultaneously with the appearance of the contractile ring in cytokinesis. Inhibiting RhoA activity and contractile ring assembly with C3 transferase, caused mitochondrial mislocalisation during division.ConclusionsTaken together, the data suggest a model in which mitochondria are transported by a microtubule-mediated mechanism involving equatorial astral microtubules, Miro-1, and KIF5B to the nascent actomyosin contractile ring in cytokinesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13008-016-0015-4) contains supplementary material, which is available to authorized users.

Highlights

The role of the cytoskeleton in regulating mitochondrial distribution in dividing mammalian cells is poorly understood
We recently reported that mitochondria localize to the cleavage furrow during cytokinesis in mammalian cells using a mechanism that is dependent on microtubules of the mitotic spindle [15]
Mitochondria associate with astral microtubules during cytokinesis We previously demonstrated that mitochondria are transported to the cleavage furrow in a microtubuledependent manner [15, 26]

Summary

Introduction

The role of the cytoskeleton in regulating mitochondrial distribution in dividing mammalian cells is poorly understood. We previously demonstrated that mitochondria are transported to the cleavage furrow during cytokinesis in a microtubule-dependent manner. The exact subset of spindle microtubules and molecular machinery involved remains unknown. The role of the cytoskeleton and associated proteins in determining the distribution of mitochondria during cytokinesis, the final stage of cell division, is poorly understood. We recently reported that mitochondria localize to the cleavage furrow during cytokinesis in mammalian cells using a mechanism that is dependent on microtubules of the mitotic spindle [15]. While we found that mitochondrial transport to the cleavage furrow during cytokinesis was microtubule-dependent, the subset of spindle microtubules and molecular machinery remained unknown. A recent RNAi screen for new Lawrence et al Cell Div (2016) 11:3

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