Different mtDNA mutations modify tumor progression in dependence of the degree of respiratory complex I impairment

Human Molecular Genetics

Volumn 23, Issue 6, 2014, Pages 1453-1466

  Iommarini, Luisa ^a   Kurelac, Ivana ^a   Capristo, Mariantonietta ^a   Calvaruso, Maria Antonietta ^a   Giorgio, Valentina ^b,c   Bergamini, Christian ^a   Ghelli, Anna ^a   Nanni, Patrizia ^a   De giovanni, Carla ^a   Carelli, Valerio ^a,d   Fato, Romana ^a   Lollini, Pier Luigi ^a   Rugolo, Michela ^a   Gasparre, Giuseppe ^a   Porcelli, Anna Maria ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b CNR   (Italy)

^c UNIVERSITY OF PADOVA   (Italy)

^d IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AMP-ACTIVATED PROTEIN KINASES; CELL LINE, TUMOR; DISEASE PROGRESSION; DNA, MITOCHONDRIAL; ELECTRON TRANSPORT COMPLEX I; ENERGY METABOLISM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MITOCHONDRIAL PROTEINS; MUTAGENESIS, INSERTIONAL; NADH DEHYDROGENASE; OSTEOSARCOMA; OXIDATIVE PHOSPHORYLATION; POINT MUTATION; REACTIVE OXYGEN SPECIES; RNA, TRANSFER;

EID: 84894292944     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddt533     Document Type: Article

References (70)

1. Roestenberg, P., Manjeri, G.R., Valsecchi, F., Smeitink, J.A., Willems, P.H. and Koopman, W.J. (2012) Pharmacological targeting of mitochondrial complexI deficiency: the cellular level and beyond. Mitochondrion, 12, 57-65.
2. Distelmaier, F., Koopman, W.J., van den Heuvel, L.P., Rodenburg, R.J., Mayatepek, E., Willems, P.H. and Smeitink, J.A. (2009) Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain, 132, 833-842.
3. Schon, E.A., DiMauro, S. and Hirano, M. (2012) Human mitochondrial DNA: roles of inherited and somatic mutations. Nat. Rev. Genet., 13, 878-890.
4. Chandra, D. and Singh, K.K. (2011) Genetic insights into OXPHOS defect and its role in cancer. Biochim. Biophys. Acta, 1807, 620-625.
5. Patti, M.E. and Corvera, S. (2010) The role of mitochondria in the pathogenesis of type 2 diabetes. Endocr. Rev., 31, 364-395.
6. Wallace, D.C. (2012) Mitochondria and cancer. Nat. Rev. Cancer, 12, 685-698.
7. Iommarini, L., Calvaruso, M.A., Kurelac, I., Gasparre, G. and Porcelli, A.M. (2013) Complex I impairment in mitochondrial diseases and cancer: parallel roads leading to different outcomes. Int. J. Biochem. Cell Biol., 45, 47-63.
8. Gasparre, G., Porcelli, A.M., Lenaz, G. and Romeo, G. (2013) Relevance of mitochondrial genetics and metabolism in cancer development. Cold Spring Harb. Perspect. Biol., 5.
9. Dasgupta, S., Soudry, E., Mukhopadhyay, N., Shao, C., Yee, J., Lam, S., Lam, W., Zhang, W., Gazdar, A.F., Fisher, P.B. et al. (2012) Mitochondrial DNA mutations in respiratory complex-I in never-smoker lung cancer patients contribute to lung cancer progression and associated with EGFR gene mutation. J. Cell Physiol., 227, 2451-2460.
10. Ishikawa, K., Takenaga, K., Akimoto, M., Koshikawa, N., Yamaguchi, A., Imanishi, H., Nakada, K., Honma, Y. and Hayashi, J. (2008)ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science, 320, 661-664.
11. Sun, W., Zhou, S., Chang, S.S., McFate, T., Verma, A. and Califano, J.A. (2009) Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma. Clin. Cancer Res., 15, 476-484.
12. Zhou, S., Kachhap, S., Sun, W., Wu, G., Chuang, A., Poeta, L., Grumbine, L., Mithani, S.K., Chatterjee, A., Koch, W. et al. (2007) Frequency and phenotypic implications of mitochondrial DNA mutations in human squamous cell cancers of the head and neck. Proc. Natl Acad. Sci. USA, 104, 7540-7545.
13. Park, J.S., Sharma, L.K., Li, H., Xiang, R., Holstein, D., Wu, J., Lechleiter, J., Naylor, S.L., Deng, J.J., Lu, J. et al. (2009) A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis. Hum. Mol. Genet., 18, 1578-1589.
14. Gasparre, G., Kurelac, I., Capristo, M., Iommarini, L., Ghelli, A., Ceccarelli, C., Nicoletti, G., Nanni, P., De Giovanni, C., Scotlandi, K. et al. (2011) A mutation threshold distinguishes the antitumorigenic effects of the mitochondrial gene MTND1, an oncojanus function. Cancer Res., 71, 6220-6229.
15. Calabrese, C., Iommarini, L., Kurelac, I., Calvaruso, M.A., Capristo, M., Lollini, P.L., Nanni, P., Bergamini, C., Nicoletti, G., De Giovanni, C. et al. (2013) Respiratory complex I is essential to induce a Warburg profile in mitochondria-defective tumor cells. Cancer Metab., 1:11.
16. Sharma, L.K., Fang, H., Liu, J., Vartak, R., Deng, J. and Bai, Y. (2011) Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation. Hum. Mol. Genet., 20, 4605-4616.
17. Memmott, R.M. and Dennis, P.A. (2009) Akt-dependent and -independent mechanisms of mTOR regulation in cancer. Cell Signal., 21, 656-664.
18. Schultze, S.M., Hemmings, B.A., Niessen, M. and Tschopp, O. (2012) PI3K/AKT, MAPKandAMPKsignalling: protein kinases in glucose homeostasis. Expert Rev. Mol. Med., 14, e1.
19. Majmundar, A.J., Wong, W.J. and Simon, M.C. (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell, 40, 294-309.
20. Huoponen, K., Vilkki, J., Aula, P., Nikoskelainen, E.K. and Savontaus, M.L. (1991) A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy. Am. J. Hum. Genet., 48, 1147-1153.
21. Goto, Y., Nonaka, I. and Horai, S. (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature, 348, 651-653.
22. Mariotti, C., Savarese, N., Suomalainen, A., Rimoldi, M., Comi, G., Prelle, A., Antozzi, C., Servidei, S., Jarre, L., DiDonato, S. et al. (1995) Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA. J. Neurol., 242, 304-312.
23. Gasparre, G., Hervouet, E., de Laplanche, E., Demont, J., Pennisi, L.F., Colombel, M., Mege-Lechevallier, F., Scoazec, J.Y., Bonora, E., Smeets, R. et al. (2008) Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma. Hum. Mol. Genet., 17, 986-995.
24. Gasparre, G., Porcelli, A.M., Bonora, E., Pennisi, L.F., Toller, M., Iommarini, L., Ghelli, A., Moretti, M., Betts, C.M., Martinelli, G.N. et al. (2007) Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc. Natl Acad. Sci. USA, 104, 9001-9006.
25. Kurelac, I., MacKay, A., Lambros, M.B., Di Cesare, E., Cenacchi, G., Ceccarelli, C., Morra, I., Melcarne, A., Morandi, L., Calabrese, F.M. et al. (2013) Somatic complex I disruptive mitochondrial DNA mutations are modifiers of tumorigenesis that correlate with low genomic instability in pituitary adenomas. Hum. Mol. Genet., 22, 226-238.
26. DeBerardinis, R.J., Lum, J.J., Hatzivassiliou, G. and Thompson, C.B. (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab., 7, 11-20.
27. Hardie, D.G. and Hawley, S.A. (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. Bioessays, 23, 1112-1119.
28. Sanders, M.J., Grondin, P.O., Hegarty, B.D., Snowden, M.A. and Carling, D. (2007) Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem. J., 403, 139-148.
29. Hardie, D.G. and Pan, D.A. (2002) Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem. Soc. Trans., 30, 1064-1070.
30. Beretta, S., Mattavelli, L., Sala, G., Tremolizzo, L., Schapira, A.H., Martinuzzi, A., Carelli, V. and Ferrarese, C. (2004) Leber hereditary optic neuropathy mtDNA mutations disrupt glutamate transport in cybrid cell lines. Brain, 127, 2183-2192.
31. Wong, A., Cavelier, L., Collins-Schramm, H.E., Seldin, M.F., McGrogan, M., Savontaus, M.L. and Cortopassi, G.A. (2002) Differentiation-specific effects of LHON mutations introduced into neuronal NT2 cells. Hum. Mol. Genet., 11, 431-438.
32. Pereira, L., Soares, P., Maximo, V. and Samuels, D.C. (2012) Somatic mitochondrialDNAmutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors. BMCCancer, 12, 53.
33. He, Y., Wu, J., Dressman, D.C., Iacobuzio-Donahue, C., Markowitz, S.D., Velculescu, V.E., Diaz, L.A. Jr., Kinzler, K.W., Vogelstein, B. and Papadopoulos, N. (2010) Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature, 464, 610-614.
34. Payne, B.A., Wilson, I.J., Yu-Wai-Man, P., Coxhead, J., Deehan, D., Horvath, R., Taylor, R.W., Samuels, D.C., Santibanez-Koref, M. and Chinnery, P.F. (2013) Universal heteroplasmy of human mitochondrial DNA. Hum. Mol. Genet., 22, 384-390.
35. Petros, J.A., Baumann, A.K., Ruiz-Pesini, E., Amin, M.B., Sun, C.Q., Hall, J., Lim, S., Issa, M.M., Flanders, W.D., Hosseini, S.H. et al. (2005) mtDNA mutations increase tumorigenicity in prostate cancer. Proc. Natl Acad. Sci. USA, 102, 719-724.
36. Shidara, Y., Yamagata, K., Kanamori, T., Nakano, K., Kwong, J.Q., Manfredi, G., Oda, H. and Ohta, S. (2005) Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res., 65, 1655-1663.
37. Larman, T.C., DePalma, S.R., Hadjipanayis, A.G., Protopopov, A., Zhang, J., Gabriel, S.B., Chin, L., Seidman, C.E., Kucherlapati, R. and Seidman, J.G. (2012) Spectrum of somatic mitochondrial mutations in five cancers. Proc. Natl Acad. Sci. USA, 109, 14087-14091.
38. Lu, J., Sharma, L.K. and Bai, Y. (2009) Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res., 19, 802-815.
39. Abu-Amero, K., Zou, M. and Shi, Y. (2004) Mitochondrial A135149 mutation without MELAS but in association with papillary thyroid carcinoma. Clin. Genet., 66, 569-570.
40. Lorenc, A., Bryk, J., Golik, P., Kupryjanczyk, J., Ostrowski, J., Pronicki, M., Semczuk, A., Szolkowska, M. and Bartnik, E. (2003)HomoplasmicMELAS A3243G mtDNA mutation in a colon cancer sample. Mitochondrion, 3, 119-124.
41. Meierhofer, D., Ebner, S., Mayr, J.A., Jones, N.D., Kofler, B. and Sperl, W. (2006) Platelet transfusion canmimic somaticmtDNAmutations. Leukemia, 20, 362-363.
42. Chandel, N.S., McClintock, D.S., Feliciano, C.E., Wood, T.M., Melendez, J.A., Rodriguez, A.M. and Schumacker, P.T. (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J. Biol. Chem., 275, 25130-25138.
43. Guzy, R.D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K.D., Simon, M.C., Hammerling, U. and Schumacker, P.T. (2005) Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab., 1, 401-408.
44. Mansfield, K.D., Simon, M.C. and Keith, B. (2004) Hypoxic reduction in cellular glutathione levels requires mitochondrial reactive oxygen species. J. Appl. Physiol., 97, 1358-1366.
45. Sullivan, L.B., Martinez-Garcia, E., Nguyen, H., Mullen, A.R., Dufour, E., Sudarshan, S., Licht, J.D., Deberardinis, R.J. and Chandel, N.S. (2013) The proto-oncometabolite fumarate binds glutathione to amplify ROS-dependent signaling. Mol. Cell., 51, 236-248.
46. Srinivas, V., Leshchinsky, I., Sang, N., King, M.P., Minchenko, A. and Caro, J. (2001) Oxygen sensing and HIF-1 activation does not require an active mitochondrial respiratory chain electron-transfer pathway. J. Biol. Chem., 276, 21995-21998.
47. Koshikawa, N., Hayashi, J., Nakagawara, A. and Takenaga, K. (2009) Reactive oxygen species-generating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-1alpha gene transcription via phosphatidylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway. J. Biol. Chem., 284, 33185-33194.
48. Lenaz, G., Baracca, A., Carelli, V., D'Aurelio, M., Sgarbi, G. and Solaini, G. (2004) Bioenergetics of mitochondrial diseases associated with mtDNA mutations. Biochim. Biophys. Acta, 1658, 89-94.
49. Hardie, D.G. (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat. Rev. Mol. Cell Biol., 8, 774-785.
50. Hemminki, A., Markie, D., Tomlinson, I., Avizienyte, E., Roth, S., Loukola, A., Bignell, G., Warren, W., Aminoff, M., Hoglund, P. et al. (1998)Aserine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature, 391, 184-187.
51. Shackelford, D.B. and Shaw, R.J. (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer, 9, 563-575.
52. van Slegtenhorst, M., de Hoogt, R., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., van den Ouweland, A., Halley, D., Young, J. et al. (1997) Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science, 277, 805-808.
53. Shackelford, D.B., Vasquez, D.S., Corbeil, J., Wu, S., Leblanc, M., Wu, C.L., Vera, D.R. and Shaw, R.J. (2009) mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome. Proc. Natl Acad. Sci. USA, 106, 11137-11142.
54. Faubert, B., Boily, G., Izreig, S., Griss, T., Samborska, B., Dong, Z., Dupuy, F., Chambers, C., Fuerth, B.J., Viollet, B. et al. (2013) AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab., 17, 113-124.
55. Isaacs, J.S., Jung, Y.J., Mole, D.R., Lee, S., Torres-Cabala, C., Chung, Y.L., Merino, M., Trepel, J., Zbar, B., Toro, J. et al. (2005) HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell, 8, 143-153.
56. Selak, M.A., Armour, S.M., MacKenzie, E.D., Boulahbel, H., Watson, D.G., Mansfield, K.D., Pan, Y., Simon, M.C., Thompson, C.B. and Gottlieb, E. (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell, 7, 77-85.
57. Tong, W.H., Sourbier, C., Kovtunovych, G., Jeong, S.Y., Vira, M., Ghosh, M., Romero, V.V., Sougrat, R., Vaulont, S., Viollet, B. et al. (2011) The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels. Cancer Cell, 20, 315-327.
58. Bonora, E., Porcelli, A.M., Gasparre, G., Biondi, A., Ghelli, A., Carelli, V., Baracca, A., Tallini, G., Martinuzzi, A., Lenaz, G. et al. (2006) Defective oxidative phosphorylation in thyroid oncocytic carcinoma is associated with pathogenic mitochondrial DNA mutations affecting complexes I and III. Cancer Res., 66, 6087-6096.
59. Carelli, V., Vergani, L., Bernazzi, B., Zampieron, C., Bucchi, L., Valentino, M., Rengo, C., Torroni, A. and Martinuzzi, A. (2002) Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy. Biochim. Biophys. Acta, 1588, 7-14.
60. Ghelli, A., Zanna, C., Porcelli, A.M., Schapira, A.H., Martinuzzi, A., Carelli, V. and Rugolo, M. (2003) Leber's hereditary optic neuropathy (LHON) pathogenic mutations induce mitochondrial-dependent apoptotic death in transmitochondrial cells incubated with galactose medium. J. Biol. Chem., 278, 4145-4150.
61. King, M.P., Koga, Y., Davidson, M. and Schon, E.A. (1992) Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Mol. Cell. Biol., 12, 480-490.
62. Porcelli, A.M., Ghelli, A., Iommarini, L., Mariani, E., Hoque, M., Zanna, C., Gasparre, G. and Rugolo, M. (2008) The antioxidant function of Bcl-2 preserves cytoskeletal stability of cells with defective respiratory complex I. Cell Mol. Life Sci., 65, 2943-2951.
63. Giorgio, V., Petronilli, V., Ghelli, A., Carelli, V., Rugolo, M., Lenaz, G. and Bernardi, P. (2012)Theeffects of idebenoneon mitochondrial bioenergetics. Biochim. Biophys. Acta, 1817, 363-369.
64. Janssen, A.J., Trijbels, F.J., Sengers, R.C., Smeitink, J.A., van den Heuvel, L.P., Wintjes, L.T., Stoltenborg-Hogenkamp, B.J. and Rodenburg, R.J. (2007) Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Clin. Chem., 53, 729-734.
65. Porcelli, A.M., Ghelli, A., Ceccarelli, C., Lang, M., Cenacchi, G., Capristo, M., Pennisi, L.F., Morra, I., Ciccarelli, E., Melcarne, A. et al. (2010) The genetic and metabolic signature of oncocytic transformation implicates HIF1alpha destabilization. Hum. Mol. Genet., 19, 1019-1032.
66. Porcelli, A.M., Angelin, A., Ghelli, A., Mariani, E., Martinuzzi, A., Carelli, V., Petronilli, V., Bernardi, P. and Rugolo, M. (2009) Respiratory complex I dysfunction due to mitochondrial DNA mutations shifts the voltage threshold for opening of the permeability transition pore toward resting levels. J. Biol. Chem., 284, 2045-2052.
67. Jones, D.P. (1981) Determination of pyridine dinucleotides in cell extracts by high-performance liquid chromatography. J. Chromatogr., 225, 446-449.
68. Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248-254.
69. Schneider, C.A., Rasband, W.S. and Eliceiri, K.W. (2012) NIH Image to Image J: 25 years of image analysis. Nat. Methods, 9, 671-675.
70. Moreno-Loshuertos, R., Acin-Perez, R., Fernandez-Silva, P., Movilla, N., Perez-Martos, A., Rodriguez de Cordoba, S., Gallardo, M.E. and Enriquez, J.A. (2006) Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants. Nat. Genet., 38, 1261-1268.