Research on Relevance Between Mitochondrial ATP Synthase and Malignant Tumor_Journal of Biomedical Engineering

Authors：

WANGJingjing ¹ , LIRuijuan ² ,  ZHANGGuangsen ²

1. Department of Oncology, Second Xiang-Ya Hospital, Central South University, Changsha 410011, China;
2. Department of Hematology, Second Xiang-Ya Hospital, Central South University, Changsha 410011, China;

Corresponding author：

ZHANGGuangsen, Email: zgsllzy@163.com

Keywords：

mitochondrial ATP synthase; the bioenergetic signature of cancer; malignant tumor; multidrug resistance

DOI：

10.7507/1001-5515.20140133

Video：

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Abstract Full text Figures/Tables Video References Cited by

Mitochondrial adenosine triphosphate (ATP) synthase is the key enzyme of mitochondrial oxidative phosphorylation reaction.The down-regulation of the mitochondrial ATP synthase is a hallmark of most human carcinomas, which is the embodiment of the bioenergetic signature of cancer in the performance of the decreased oxidative phosphorylation and increased aerobic glycolysis. Combining with the bioenergetic signature of cancer, studies showed that mitochondrial ATP synthase and multidrug resistance and adverse prognosis of tumor were closely related. Its mechanisms are related to post-transcriptional regulation of the ATP synthase,the hypermethylation of the ATP synthase gene and the inhibitor peptide of the mitochondrial ATP synthase, called ATP synthase inhibitory factor 1(IF1). In this review, we stress the biological characteristics of mitochondrial ATP synthase and the relationship between ATP synthase and multidrug resistance and prognosis of Malignant tumor, in order to find a new way for tumor therapy.

Citation： WANGJingjing, LIRuijuan, ZHANGGuangsen. Research on Relevance Between Mitochondrial ATP Synthase and Malignant Tumor. Journal of Biomedical Engineering, 2014, 31(3): 714-717. doi: 10.7507/1001-5515.20140133 Copy

1.	MATHUPALA S P, KO Y H, PEDERSEN P L. The pivotal roles of mitochondria in Cancer:Warburg and beyond and encouraging prospects for effective therapies[J]. Biochim Biophys Acta, 2010, 1797(6-7):1225-1230.
2.	WILLERS I M, ISIDORO A, ORTEGA A D, et al. Selective inhibition of β-F1-ATPase mRNA translation in human tumours[J]. Biochem J, 2010, 426:319-326.
3.	WILLERS I M, CUEZVA J M. Post-transcriptional regulation of the mitochondrial H(+)-ATP synthase:a key regulator of the metabolic phenotype in Cancer[J]. Biochim Biophys Acta, 2011, 1807(6):543-551.
4.	WATANABE R, TABATA K V, IINO R, et al. Biased brownian stepping rotation of FoF1-ATP synthase driven by proton motive force[J]. Nat Commun, 2013, 4:1631.
5.	WANG W J, SHI X X, LIU Y W, et al. The mechanism underlying the effects of the cell surface ATP synthase on the regulation of intracellular acidification during acidosis[J]. J Cell Biochem, 2013, 114(7):1695-1703.
6.	VAZQUEZ-MARTIN A, COROMINAS-FAJA B, CUFI S, et al. The mitochondrial H(+)-ATP synthase and the lipogenic Switch:new core components of metabolic reprogramming in induced pluripotent stem (iPS) cells[J]. Cell Cycle, 2013, 12(2):207-218.
7.	SÁNCHEZ-ARAGÓ M, CHAMORRO M, CUEZVA J M. Selection of Cancer cells with repressed mitochondria triggers colon Cancer progression[J]. Carcinogenesis, 2010, 31(4):567-576.
8.	KRASNOV G S, DMITRIEV A A, SNEZHKINA A V, et al. Deregulation of glycolysis in cancer:glyceraldehyde-3-phosphate dehydrogenase as a therapeutic target[J]. Expert Opin Ther Targets, 2013, 17(6):681-693.
9.	SHIN Y K, YOO B C, CHANG H J, et al. Down-regulation of mitochondrial F1F0-ATP synthase in human colon Cancer cells with induced 5-fluorouracil resistance[J]. Cancer Res, 2005, 65(8):3162-3170.
10.	LI R J, ZHANG G S, CHEN Y H, et al. Down-regulation of mitochondrial ATPase by hypermethylation mechanism in chronic myeloid leukemia is associated with multidrug resistance[J]. Ann Oncol, 2010, 21(7):1506-1514.
11.	HERNLUND E, HJERPE E, AVALL-LUNDQVIST E, et al. Ovarian carcinoma cells with low levels of beta-F1-ATPase are sensitive to combined Platinum and 2-deoxy-D-glucose treatment[J]. Mol Cancer Ther, 2009, 8(7):1916-1923.
12.	LIN P C, LIN J K, YANG S H, et al. Expression of beta-F1-ATPase and mitochondrial transcription factor A and the change in mitochondrial DNA content in colorectal cancer:clinical data analysis and evidence from an in vitro study[J]. Int J Colorectal Dis, 2008, 23(12):1223-1232.
13.	SÁNCHEZ-ARAGÓ M, FORMENTINI L, CUEZVA J M. Mitochondria-mediated energy adaption in cancer:the H(+)-ATP synthase-geared switch of metabolism in human tumors[J]. Antioxid Redox Signal, 2012, 24.
14.	CREANEY J, DICK I M, YEOMAN D, et al. Auto-antibodies to β-F1-ATPase and vimentin in malignant mesothelioma[J]. PLoS One, 2011, 6(10):e26515.
15.	SÁNCHEZ-ARAGÓ M, CUEZVA J M. The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate,iodoacetate or 5-fluorouracil[J]. J Transl Med, 2011, 9:19.
16.	SUN R C, BOARD P G, BLACKBURN A C. Targeting metabolism with arsenic trioxide and dichloroacetate in breast cancer cells[J]. Mol Cancer, 2011, 10:142.
17.	WILLERS I M, MARTÍNEZ-REYES I, MARTÍNEZ-DIEZ M, et al. miR-127-5p targets the 3'UTR of human β-F1-ATPase mRNA and inhibits its translation[J]. Biochim Biophys Acta, 2012, 1817(5):838-848.
18.	ORTEGA A D, SALA S, ESPINOSA E, et al. HuR and the bioenergetic signature of breast cancer:a low tumor expression of the RNA-binding protein predicts a higher risk of disease recurrence[J]. Carcinogenesis, 2008, 29(11):2053-2061.
19.	ORTEGA A D, WILLERS I M, SALA S, et al. Human G3BP1 interacts with beta-F1-ATPase mRNA and inhibits its translation[J]. J Cell Sci, 2010, 123(Pt 16):2685-2696.
20.	FUJIKAWA M, IMAMURA H, NAKAMURA J, et al. Assessing actual contribution of IF1, inhibitor of mitochondrial FoF1, to ATP homeostasis, cell growth, mitochondrial morphology, and cell viability[J]. J Biol Chem, 2012, 287(22):18781-18787.
21.	SÁNCHEZ-CENIZO L, FORMENTINI L, ALDEA M, et al. Up-regulation of the ATPase inhibitory factor 1(IF1) of the mitochondrial H⁺-ATP synthase in human tumors mediates the metabolic shift of cancer cells to a Warburg phenotype[J]. J Biol Chem, 2010, 285(33):25308-25313.
22.	FORMENTINI L, SÁNCHEZ-ARAGÓ M, SÁNCHEZ-CENIZO L, et al. The mitochondrial ATPase inhibitory factor 1 triggers a ROS-mediated retrograde prosurvival and proliferative response[J]. Mol Cell, 2012, 45(6):731-742.
23.	DOMENIS R, BISETTO E, ROSSI D, et al. Glucose-modulated mitochondria adaptation in tumor cells:a focus on ATP synthase and inhibitor factor 1[J]. Int J Mol Sci, 2012, 13(2):1933-1950.

1. MATHUPALA S P, KO Y H, PEDERSEN P L. The pivotal roles of mitochondria in Cancer:Warburg and beyond and encouraging prospects for effective therapies[J]. Biochim Biophys Acta, 2010, 1797(6-7):1225-1230.
2. WILLERS I M, ISIDORO A, ORTEGA A D, et al. Selective inhibition of β-F1-ATPase mRNA translation in human tumours[J]. Biochem J, 2010, 426:319-326.
3. WILLERS I M, CUEZVA J M. Post-transcriptional regulation of the mitochondrial H(+)-ATP synthase:a key regulator of the metabolic phenotype in Cancer[J]. Biochim Biophys Acta, 2011, 1807(6):543-551.
4. WATANABE R, TABATA K V, IINO R, et al. Biased brownian stepping rotation of FoF1-ATP synthase driven by proton motive force[J]. Nat Commun, 2013, 4:1631.
5. WANG W J, SHI X X, LIU Y W, et al. The mechanism underlying the effects of the cell surface ATP synthase on the regulation of intracellular acidification during acidosis[J]. J Cell Biochem, 2013, 114(7):1695-1703.
6. VAZQUEZ-MARTIN A, COROMINAS-FAJA B, CUFI S, et al. The mitochondrial H(+)-ATP synthase and the lipogenic Switch:new core components of metabolic reprogramming in induced pluripotent stem (iPS) cells[J]. Cell Cycle, 2013, 12(2):207-218.
7. SÁNCHEZ-ARAGÓ M, CHAMORRO M, CUEZVA J M. Selection of Cancer cells with repressed mitochondria triggers colon Cancer progression[J]. Carcinogenesis, 2010, 31(4):567-576.
8. KRASNOV G S, DMITRIEV A A, SNEZHKINA A V, et al. Deregulation of glycolysis in cancer:glyceraldehyde-3-phosphate dehydrogenase as a therapeutic target[J]. Expert Opin Ther Targets, 2013, 17(6):681-693.
9. SHIN Y K, YOO B C, CHANG H J, et al. Down-regulation of mitochondrial F1F0-ATP synthase in human colon Cancer cells with induced 5-fluorouracil resistance[J]. Cancer Res, 2005, 65(8):3162-3170.
10. LI R J, ZHANG G S, CHEN Y H, et al. Down-regulation of mitochondrial ATPase by hypermethylation mechanism in chronic myeloid leukemia is associated with multidrug resistance[J]. Ann Oncol, 2010, 21(7):1506-1514.
11. HERNLUND E, HJERPE E, AVALL-LUNDQVIST E, et al. Ovarian carcinoma cells with low levels of beta-F1-ATPase are sensitive to combined Platinum and 2-deoxy-D-glucose treatment[J]. Mol Cancer Ther, 2009, 8(7):1916-1923.
12. LIN P C, LIN J K, YANG S H, et al. Expression of beta-F1-ATPase and mitochondrial transcription factor A and the change in mitochondrial DNA content in colorectal cancer:clinical data analysis and evidence from an in vitro study[J]. Int J Colorectal Dis, 2008, 23(12):1223-1232.
13. SÁNCHEZ-ARAGÓ M, FORMENTINI L, CUEZVA J M. Mitochondria-mediated energy adaption in cancer:the H(+)-ATP synthase-geared switch of metabolism in human tumors[J]. Antioxid Redox Signal, 2012, 24.
14. CREANEY J, DICK I M, YEOMAN D, et al. Auto-antibodies to β-F1-ATPase and vimentin in malignant mesothelioma[J]. PLoS One, 2011, 6(10):e26515.
15. SÁNCHEZ-ARAGÓ M, CUEZVA J M. The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate,iodoacetate or 5-fluorouracil[J]. J Transl Med, 2011, 9:19.
16. SUN R C, BOARD P G, BLACKBURN A C. Targeting metabolism with arsenic trioxide and dichloroacetate in breast cancer cells[J]. Mol Cancer, 2011, 10:142.
17. WILLERS I M, MARTÍNEZ-REYES I, MARTÍNEZ-DIEZ M, et al. miR-127-5p targets the 3'UTR of human β-F1-ATPase mRNA and inhibits its translation[J]. Biochim Biophys Acta, 2012, 1817(5):838-848.
18. ORTEGA A D, SALA S, ESPINOSA E, et al. HuR and the bioenergetic signature of breast cancer:a low tumor expression of the RNA-binding protein predicts a higher risk of disease recurrence[J]. Carcinogenesis, 2008, 29(11):2053-2061.
19. ORTEGA A D, WILLERS I M, SALA S, et al. Human G3BP1 interacts with beta-F1-ATPase mRNA and inhibits its translation[J]. J Cell Sci, 2010, 123(Pt 16):2685-2696.
20. FUJIKAWA M, IMAMURA H, NAKAMURA J, et al. Assessing actual contribution of IF1, inhibitor of mitochondrial FoF1, to ATP homeostasis, cell growth, mitochondrial morphology, and cell viability[J]. J Biol Chem, 2012, 287(22):18781-18787.
21. SÁNCHEZ-CENIZO L, FORMENTINI L, ALDEA M, et al. Up-regulation of the ATPase inhibitory factor 1(IF1) of the mitochondrial H⁺-ATP synthase in human tumors mediates the metabolic shift of cancer cells to a Warburg phenotype[J]. J Biol Chem, 2010, 285(33):25308-25313.
22. FORMENTINI L, SÁNCHEZ-ARAGÓ M, SÁNCHEZ-CENIZO L, et al. The mitochondrial ATPase inhibitory factor 1 triggers a ROS-mediated retrograde prosurvival and proliferative response[J]. Mol Cell, 2012, 45(6):731-742.
23. DOMENIS R, BISETTO E, ROSSI D, et al. Glucose-modulated mitochondria adaptation in tumor cells:a focus on ATP synthase and inhibitor factor 1[J]. Int J Mol Sci, 2012, 13(2):1933-1950.

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