[1]袁荣美,丁 祥,谭秀梅,等.线粒体外膜转位酶基因tom70缺失对裂殖酵母细胞动力学的影响[J].南京师范大学学报(自然科学版),2020,43(03):120-128.[doi:10.3969/j.issn.1001-4616.2020.03.019]
 Yuan Rongmei,Ding Xiang,Tan Xiumei,et al.Loss of tom70(Translocase of Outer Mitochondrial 70)Results in Changes of Cell Dynamics in Fission Yeast[J].Journal of Nanjing Normal University(Natural Science Edition),2020,43(03):120-128.[doi:10.3969/j.issn.1001-4616.2020.03.019]





Loss of tom70(Translocase of Outer Mitochondrial 70)Results in Changes of Cell Dynamics in Fission Yeast
袁荣美1丁 祥2谭秀梅1侯怡铃1
(1.西华师范大学生命科学学院,西南野生动植物资源保护教育部重点实验室,四川 南充 637009)(2.西华师范大学环境科学与工程学院,四川 南充 637009)
Yuan Rongmei1Ding Xiang2Tan Xiumei1Hou Yiling1
(1.College of Life Sciences,China West Normal University,Key Laboratory of Southwest China Wildlife ResourcesConservation(Ministry of Education),Nanchong 637009,China)(2.College of Environmental Science and Engineering,China West Normal University,Nanchong 637009,China)
tom70mitosiscell cyclecell dynamicsmicrotubule
tom70基因编码的是线粒体外膜转运酶(Translocase of Outer Mitochondrial,TOM)复合物中的Tom70受体,在线粒体蛋白转入线粒体膜间隙中具有重要作用. 该研究以裂殖酵母(Schizosaccharomyces pombe)为材料,采用活细胞成像的方法,研究tom70基因缺失后细胞有丝分裂中动力学的变化. 研究结果表明,tom70基因缺失会导致细胞间期微管数目和长度异常,tom70Δ细胞中微管长度长于野生型; 同时,细胞进入分裂期时tom70Δ纺锤体的形成、生长速率、生长时间、长度和断裂方式都与野生型存在差异. 纺锤体长度统计显示tom70Δ细胞存在纺锤体延迟断裂现象. 对tom70Δ进行活细胞成像,观察3种不同的纺锤体断裂行为:直线型、拱形和S型. 综上结果表明,线粒体tom70基因缺失导致细胞动力学缺陷,包括纺锤体维持缺陷、染色体分离缺陷和纺锤体断裂缺陷.
The tom70 encodes the tom70 receptor of the complex of translocase of outer mitochondrial,which plays an important role in the transfer of mitochondrial protein into the mitochondrial membrane space. Schizosaccharomyces pombe was used as material to study the dynamic changes of cell mitosis after tom70 gene deletion. The results showed that the number and length of microtubules were abnormal in the interphase,and the length of microtubules was longer in the tom70Δ cells than in the wild type. At the same time,the formation,growth rate,growth time,length and fracture mode of the spindle were different from those in the wild type. The statistics of spindle length showed that there was a phenomenon of delayed spindle rupture in the tom70Δ cells. Three kinds of spindle fracture behaviors were observed,linear,arched and S-shaped. The results showed that the deletion of mitochondrial tom70 gene led to the defects of cell dynamics,including spindle maintenance,chromosome separation and spindle breakage.


[1] WESTERMANN B,NEUPERT W. “Omics”of the mitochondrion[J]. Nature biotechnology,2003,21(3):239-240.
[2]FAN A C,GAVA L M,RAMOS C H,et al. Human mitochondrial import receptor Tom70 functions as a monomer[J]. Biochemical journal,2010,429(3):553-563.
[3]MARTENSSON C U,PRIENITZ C,SONG J,et al. Mitochondrial protein translocation-associated degradation[J]. Nature,2019,569(7758):679-683.
[4]FILADI R,LEAL N S,SCHREINER B,et al. TOM70 sustains cell bioenergetics by promoting IP3R3-mediated ER to mitochondria Ca2+ transfer[J]. Current biology,2018,28(3):369-382.
[5]STUART R A,ONO H,LANGER T,et al. Mechanisms of protein import into mitochondria[J]. Cell structure function,1996,21(5):403-406.
[6]MELIN J,KILISCH M,NEUMANN P,et al. A presequence-binding groove in Tom70 supports import of Mdl1 into mitochondria[J]. Biochimica et biophysica acta,2015,1853(8):1850-1859.
[7]FAN A C,BHANGOO M K,YOUNG J C. Hsp90 functions in the targeting and outer membrane translocation steps of Tom70-mediated mitochondrial import[J]. Journal of biological chemistry,2006,281(44):33313-33324.
[8]LIU N N,HAN T X,DU L L,et al. A genome-wide screen for Schizosaccharomyces pombe deletion mutants that affect telomere length[J]. Cell research,2010,20(8):963-975.
[9]MALECKI M,BITTON D A,RODRIGUEZ-LOPEZ M,et al. Functional and regulatory profiling of energy metabolism in fission yeast[J]. Genome biology,2016,17(1):240-257.
[10]SIDERI T,RALLIS C,BITTON D A,et al. Parallel profiling of fission yeast deletion mutants for proliferation and for lifespan during long-term quiescence[J]. G3(Bethesda),2015,5(1):145-55.
[11]KENNEDY P J,VASHISHT A A,HOE K L,et al. A genome-wide screen of genes involved in cadmium tolerance in Schizosaccharomyces pombe[J]. Toxicological sciences,2008,106(1):124-39.
[12]GUO L,GANGULY A,SUN L,et al. Global fitness profiling identifies arsenic and cadmium tolerance mechanisms in fission yeast[J]. G3(Bethesda),2016,6(10):3317-3333.
[13]BURR R,STEWART E V,SHAO W,et al. Mga2 transcription factor regulates an oxygen-responsive lipid homeostasis pathway in fission yeast[J]. Journal of biological chemistry,2016,291(23):12171-12183.
[14]ZUIN A,GABRIELLI N,CALVO I A,et al. Mitochondrial dysfunction increases oxidative stress and decreases chronological life span in fission yeast[J]. PLoS one,2008,30; 3(7):e2842.
[15]BROOKHEART R T,LEE C Y,ESPENSHADE P J. Casein kinase 1 regulates sterol regulatory element-binding protein(SREBP)to control sterol homeostasis[J]. Journal of biological chemistry,2014,289(5):2725-2735.
[16]DUDIN O,MERLINI L,BENDEZU F O,et al. A systematic screen for morphological abnormalities during fission yeast sexual reproduction identifies a mechanism of actin aster formation for cell fusion[J]. PLoS genetics,2017,13(4):e1006721.
[17]COLM J R,ASSEN R,KRISTIN P,et al. Hierarchical modularity and the evolution of genetic interactomes across species[J]. Molecular cell,2012,46(5):691-704.
[18]MELKOV A,ABDU U. Regulation of long-distance transport of mitochondria along microtubules[J]. Cellular and molecular life sciences,2018,75(2):163-176.
[19]FU C,JAIN D,COSTA J,et al. mmb1p binds mitochondria to dynamic microtubules[J]. Current biology,2011,21(17):1431-1439.
[20]DESAI A,MITCHISON T J. Microtubule polymerization dynamics[J]. Annual review of cell and developmental biology,1997,13:83-117.
[21]VIRVE C,CATERINA F,MARCELLO D’A. Key role of mitochondria in alzheimer’s disease synaptic dysfunction[J]. Current pharmaceutical design,2013,19(36):6440-6450.
[22]SANTOS A,WERNERSSON R,JENSEN L J. Cyclebase 3.0:a multi-organism database on cell-cycle regulation and phenotypes[J]. Nucleic acids research,2014,43(Database issue):D1140-D1144.
[23]LI C,BAI J,HAO X,et al. Multi-gene fluorescence in situ hybridization to detect cell cycle gene copy number aberrations in young breast cancer patients[J]. Cell cycle,2014,13:1299-1305.
[24]GOMEZ E B,FORSBUR S L. Analysis of the fission Yeast Schizosaccharomyces pombe cell cycle[J]. Methods in molecular biology,2004,241:93-111.
[25]BAHLER J,WU J Q,LONGTINE M S,et al. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe[J]. Yeast,1998,14(10):943-951.
[26]RINCON S A,LAMSON A,BLACKWELL R,et al. Kinesin-5-independent mitotic spindle assembly requires the antiparallel microtubule crosslinker Ase1 in fission yeast[J]. Nature communications,2017,17:15286-15297.
[27]FORSBUR S L,RHIND N. Basic methods for fission yeast[J]. Yeast,2006,23(3):173-183.
[28]XUE Q,PEI H,LIU Q,et al. MICU1 protects against myocardial ischemia/reperfusion injury and its control by the importer receptor Tom70[J]. Cell death & disease,2017,8(7):e2923.
[29]LI J,QI M,LI C,et al. Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy[J]. Cell research,2014,24(8):977-993.
[30]DESAI A,MITCHISON T J. Microtubule polymerization dynamics[J]. Annual review of cell and developmental biology,1997,13:83-117.
[31]AVILA J. Microtubule functions[J]. Life sciences,1992,50(5):327-334.
[32]MCINTOSH J R. Assessing the contributions of motor enzymes and microtubule dynamics to mitotic chromosome motions[J]. Annual review of cell and developmental biology,2017,33:1-22.
[33]CARTELLI D,CAPPEELLEETTI G. Microtubule destabilization paves the way to Parkinson’s disease[J]. Molecular neurobiology,2017,54(9):6762-6774.
[34]CARTELLI D,GOLDWURM S,CASAGRANDE F,et al. Microtubule destabilization is shared by genetic and idiopathic Parkinson’s disease patient fibroblasts[J]. PLoS one,2012,7(5):e37467.
[35]PELLEGRINI L,WETZEL A,GRANNO S,et al. Back to the tubule:microtubule dynamics in Parkinson’s disease[J]. Cellular and molecular life sciences,2017,74(3):409-434.
[36]KKUGER L K,SANCHEZ J L,PAOLETTI A,et al. Kinesin-6 regulates cell-size-dependent spindle elongation velocity to keep mitosis duration constant in fission yeast[J]. Elife,2019,8:e42182.
[37]ARAUJO A R,GELENS L,SHERIFFF R S,et al. Positive feedback keeps duration of mitosis temporally insulated from upstream cell-cycle events[J]. Molecular cell,2016,64(2):362-375.


通讯作者:侯怡铃,博士,教授,研究方向:生物化学与分子生物学研究. E-mail:starthlh@126.com.
更新日期/Last Update: 2020-09-15