Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondria! DNA-deficient cancer cells

被引：204

作者：

Dong, Lan-Feng ^{[1
]}

Kovarova, Jaromira ^{[2
]}

Bajzikova, Martina ^{[2
]}

Bezawork-Geleta, Ayenachew ^{[1
]}

Svec, David ^{[2
]}

Endaya, Berwini ^{[1
]}

Sachaphibulkij, Karishma ^{[1
]}

Coelho, Ana R. ^{[2
,3
]}

Sebkova, Natasa ^{[1
,4
]}

Ruzickova, Anna ^{[2
]}

Tan, An S. ^{[5
]}

Kluckova, Katarina ^{[2
]}

Judasova, Kristyna ^{[2
]}

Zamecnikova, Katerina ^{[2
,6
]}

Rychtarcikova, Zuzana ^{[2
,7
]}

Gopalan, Vinod ^{[1
,8
]}

Andera, Ladislav ^{[2
]}

Sobol, Margarita ^{[9
]}

Yan, Bing ^{[1
]}

Pattnaik, Bijay ^{[10
]}

Bhatraju, Naveen ^{[10
]}

Truksa, Jaroslav ^{[2
]}

Stopka, Pavel ^{[4
]}

Hozak, Pavel ^{[9
]}

Lam, Alfred K. ^{[8
]}

Sedlacek, Radislav ^{[9
]}

Oliveira, Paulo J. ^{[3
]}

Kubista, Mikael ^{[2
,11
]}

Agrawal, Anurag ^{[10
]}

Dvorakova-Hortova, Katerina ^{[2
,4
]}

Rohlena, Jakub ^{[2
]}

Berridge, Michael V. ^{[5
]}

Neuzil, Jiri ^{[1
,2
]}

机构：

[1] Griffith Univ, Sch Med Sci, Southport, Qld, Australia

[2] Czech Acad Sci, Inst Biotechnol, Prague, Czech Republic

[3] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Cantanhede, Portugal

[4] Charles Univ Prague, Fac Sci, Dept Zool, Prague, Czech Republic

[5] Malaghan Inst Med Res, Wellington, New Zealand

[6] Zittau Goerlitz Univ Appl Sci, Zittau, Germany

[7] Charles Univ Prague, Fac Pharm, Hradec Kralove, Czech Republic

[8] Griffith Univ, Sch Med, Southport, Qld, Australia

[9] Czech Acad Sci, Inst Mol Genet, Prague, Czech Republic

[10] CSIR Inst Genom & Integrat Biol, New Delhi, India

[11] TATAA Bioctr, Gothenburg, Sweden

来源：

ELIFE | 2017年 / 6卷

基金：

澳大利亚研究理事会;

关键词：

OXIDATIVE-PHOSPHORYLATION; STROMAL CELLS; GENE-TRANSFER; TRANSPORT; METABOLISM; COMPLEX; GENOME; RESPIRATION; METASTASIS; MUTATIONS;

D O I：

10.7554/eLife.22187

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (rho(0) cells) is linked to the acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether the transfer of mtDNA involves whole mitochondria, we injected B16 rho(0) mouse melanoma cells into syngeneic C576116N(su9DsRed2) mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration. Additionally, knockdown of key mitochondrial complex I (NDUFV1) and complex II (SDHC) subunits by shRNA in B16 rho(0) cells abolished or significantly retarded their ability to form tumours. Collectively, these results show that intact mitochondria with their mtDNA payload are transferred in the developing tumour, and provide functional evidence for an essential role of oxidative phosphorylation in cancer.

引用

页数：22

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