Mitochondrial Genome Acquisition Restores Respiratory Function and Tumorigenic Potential of Cancer Cells without Mitochondrial DNA

被引：591

作者：

Tan, An S. ^{[1
]}

Baty, James W. ^{[1
]}

Dong, Lan-Feng ^{[2
]}

Bezawork-Geleta, Ayenachew ^{[2
]}

Endaya, Berwini ^{[2
]}

Goodwin, Jacob ^{[2
]}

Bajzikova, Martina ^{[3
]}

Kovarova, Jaromira ^{[3
]}

Peterka, Martin ^{[3
]}

Yan, Bing ^{[2
]}

Pesdar, Elham Alizadeh ^{[2
]}

Sobol, Margarita ^{[4
]}

Filimonenko, Anatolyj ^{[4
]}

Stuart, Shani ^{[5
]}

Vondrusova, Magdalena ^{[3
]}

Kluckova, Katarina ^{[3
]}

Sachaphibulkij, Karishma ^{[2
]}

Rohlena, Jakub ^{[3
]}

Hozak, Pavel ^{[4
]}

Truksa, Jaroslav ^{[3
]}

Eccles, David ^{[1
]}

Haupt, Larisa M. ^{[5
]}

Griffiths, Lyn R. ^{[5
]}

Neuzil, Jiri ^{[2
,3
]}

Berridge, Michael V. ^{[1
]}

机构：

[1] Malaghan Inst Med Res, Wellington 6242, New Zealand

[2] Griffith Univ, Sch Med Sci, Southport, Qld 4222, Australia

[3] Acad Sci Czech Republ, Inst Biotechnol, Prague 14220, Czech Republic

[4] Acad Sci Czech Republ, Inst Mol Genet, CR-14220 Prague, Czech Republic

[5] Queensland Univ Technol, Genom Res Ctr, Inst Hlth & Biomed Innovat, Kelvin Grove, Qld 4059, Australia

来源：

CELL METABOLISM | 2015年 / 21卷 / 01期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

ELECTRON-TRANSPORT; MUTATIONS; METABOLISM; MTDNA; SUPERCOMPLEXES; NANOTUBES; DEPLETION;

D O I：

10.1016/j.cmet.2014.12.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We report that tumor cells without mitochondrial DNA (mtDNA) show delayed tumor growth, and that tumor formation is associated with acquisition of mtDNA from host cells. This leads to partial recovery of mitochondrial function in cells derived from primary tumors grown from cells without mtDNA and a shorter lag in tumor growth. Cell lines from circulating tumor cells showed further recovery of mitochondrial respiration and an intermediate lag to tumor growth, while cells from lung metastases exhibited full restoration of respiratory function and no lag in tumor growth. Stepwise assembly of mitochondrial respiratory (super) complexes was correlated with acquisition of respiratory function. Our findings indicate horizontal transfer of mtDNA from host cells in the tumor microenvironment to tumor cells with compromised respiratory function to reestablish respiration and tumor-initiating efficacy. These results suggest pathophysiological processes for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.

引用

页码：81 / 94

页数：14

共 59 条

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