through a genome - wide small interfering rna ( sirna ) screen in hela cells , we systematically identified factors in human cells that mediate the cellular response to taxol . as expected , these factors belong to the spindle checkpoint network and the intrinsic mitochondrial apoptotic network , among other networks . we were intrigued by the lack of involvement of other molecular pathways ( e.g. , autophagy ) in the taxol response , and tested whether apoptosis and adaptation were the only 2 major exit pathways for mitotically arrested cells . mitotic duration in the presence of taxol varies depending on the cell type , but does not typically last longer than 20  hours . after this prolonged mitotic arrest , cells either undergo adaptation or apoptosis , at least in the cell lines we tested . blocking both adaptation and this striking result suggests that apoptosis and adaptation are the only 2 major fates for a cell arrested in mitosis . indeed , autophagy appeared to be suppressed during taxol - triggered mitotic arrest in rpe1 cells ( fig . 1a ) . 
 figure 1.mitochondria-dependent crosstalk between apoptosis and adaptation in response to mitotic arrest . lysates from log - phase or taxol - arrested rpe1 cells in normal medium ( dulbecco 's modified eagle medium ; dmem ) or under starvation conditions ( earl 's balanced salt solution ; ebss ) in the presence or absence of chloroquine ( cq ) were blotted with anti - lc3 ( map1lc3a / b ) or anti - tubulin ( as loading control ) antibodies . the positions of lc3-i and lc3-ii ( as an indicator of autophagy ) are indicated . unlike log - phase cells , taxol - treated cells did not show an increase in lc3-ii formation in response to starvation and cq , suggesting that autophagy might be suppressed under these conditions . the master mitotic kinase cyclin b1 ( ccnb1)cyclin dependent kinase 1 ( cdk1 ) regulates mitochondrial fission and activity by phosphorylating dynamin 1-like protein ( dnm1l or drp1 ) and components of complex i. conversely , mitochondrial activity might impact mitotic events by providing energy for spindle dynamics , chromosome movement , signaling cascades , and the continuous transcription and translation of mitotic proteins , such as cyclin b1 . during a prolonged mitotic arrest , whether a cell undergoes apoptosis or adaptation is likely a result of complicated interplay between these pathways . diminishing cyclin b1 levels during adaptation will likely produce changes in mitochondrial structure and function that affect apoptosis . lysates from log - phase or taxol - arrested rpe1 cells in normal medium ( dulbecco 's modified eagle medium ; dmem ) or under starvation conditions ( earl 's balanced salt solution ; ebss ) in the presence or absence of chloroquine ( cq ) were blotted with anti - lc3 ( map1lc3a / b ) or anti - tubulin ( as loading control ) antibodies . the positions of lc3-i and lc3-ii ( as an indicator of autophagy ) are indicated . unlike log - phase cells , taxol - treated cells did not show an increase in lc3-ii formation in response to starvation and cq , suggesting that autophagy might be suppressed under these conditions . the master mitotic kinase cyclin b1 ( ccnb1)cyclin dependent kinase 1 ( cdk1 ) regulates mitochondrial fission and activity by phosphorylating dynamin 1-like protein ( dnm1l or drp1 ) and components of complex i. conversely , mitochondrial activity might impact mitotic events by providing energy for spindle dynamics , chromosome movement , signaling cascades , and the continuous transcription and translation of mitotic proteins , such as cyclin b1 . during a prolonged mitotic arrest , whether a cell undergoes apoptosis or adaptation is likely a result of complicated interplay between these pathways . diminishing cyclin b1 levels during adaptation will likely produce changes in mitochondrial structure and function that affect apoptosis . it has been argued that the apoptosis and adaptation pathways act independently of each other during mitotic arrest . depending on which pathway is executed faster , cells preferably undergo apoptosis or adaptation . for example , adaptation is expected to be the faster process and the more frequent fate in u2os and rpe1 cells . a strong prediction of this  molecular race  model is that blocking the slower apoptosis pathway should not have a major effect on the kinetics of the faster adaptation pathway . in contrast to this expected outcome , depletion of 2 key apoptosis regulators bcl2-associated x protein ( bax ) and bcl2-antagonist / killer 1 ( bak1 ) in u2os or rpe1 cells lengthens mitotic duration and delays adaptation . this unexpected result suggests the existence of crosstalk between the apoptosis and adaptation pathways during mitotic arrest . disrupting the apoptosis pathway at different steps further reveals that this crosstalk occurs upstream of mitochondrial outer membrane permeabilization ( momp ) , an initiating event during apoptosis . although our work implicates the involvement of mitochondria in coupling mitotic apoptosis and adaptation , the detailed mechanisms remain elusive . phosphorylation of dynamin 1-like ( dnm1l , best known as drp1 ) by cyclin b1cyclin - dependent kinase 1 ( cdk1 ) promotes mitochondrial fission . cyclin b1cdk1 also modulates mitochondrial function during g2/m by phosphorylating components of the respiratory chain . intriguingly , we showed that , similar to bax / bak1 depletion , depletion or chemical inhibition of drp1 , a dynamin - like mitochondrial fission factor , also delayed adaptation in u2os cells . our results suggest that the converse might also be true : i.e. , mitochondrial fission and function might regulate mitosis . modulation of mitochondrial fission or fitness can influence the duration of taxol - induced mitotic arrest . one mechanism by which mitochondrial function could affect adaptation is by influencing cyclin b1 production . impairment of mitochondrial fitness during a prolonged mitotic arrest , as a result of continual drp1-mediated fission or partial mitochondrial permeabilization by proapoptotic proteins , could compromise energy homeostasis and impact protein translation . thus , mitochondrial fitness might be a coupling factor between the apoptosis and adaptation pathways ( fig . alternatively , components of the mitochondrial pathway could directly influence mitotic processes via physical interactions or post - translational modifications . for example , cyclin b1cdk1 has been detected in the mitochondrial matrix , and might thus be regulated directly by mitochondrial proteins . we also can not rule out other possibilities , including mitochondria - independent roles for bax , bak1 , or drp1 in mitosis . in conclusion , future studies aimed at determining the nature of this coupling will help us understand the cell - killing mechanisms of the antimitotic chemotherapeutic drugs , and ultimately lead to new strategies that can uncouple the cell death and survival pathways and increase the efficacy of these widely used antitumor drugs .
the anticancer drug taxol stabilizes microtubules and activates the spindle checkpoint , causing prolonged mitotic arrest in cancer cells . 
 our recent work suggests that the cellular decision to live or die following mitotic arrest is a complex process involving crosstalk between competing apoptotic and adaptation pathways .