Rapamycin drives selection against a pathogenic heteroplasmic mitochondrial DNA mutation

Human Molecular Genetics

Volumn 23, Issue 3, 2014, Pages 637-647

  Dai, Ying ^a   Zheng, Kangni ^a   Clark, Joanne ^a   Swerdlow, Russell H ^b   Pulst, Stefan M ^c   Sutton, James P ^d   Shinobu, Leslie A ^e   Simon, David K ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^d Pacific Neuroscience Medical Group   (United States)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MITOCHONDRIAL DNA; RAPAMYCIN; S6 KINASE;

APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CELL DEATH; CELL LINE; CELL ORGANELLE; CELL VACUOLE; CONTROLLED STUDY; CYBRID; CYTOTOXICITY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ELECTRON MICROSCOPY; GENE MUTATION; HUMAN; HUMAN CELL; LEBER HEREDITARY OPTIC NEUROPATHY; MITOCHONDRIAL DNA DEPLETION; MITOCHONDRIAL DNA MUTATION; MITOPHAGY; PHARMACOLOGICAL PARAMETERS; PRIORITY JOURNAL; UPREGULATION;

ADENOSINE TRIPHOSPHATE; APOPTOSIS; CELL LINE; DNA, MITOCHONDRIAL; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DEGRADATION; MUTATION; OPTIC ATROPHY, HEREDITARY, LEBER; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84892465214     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddt450     Document Type: Article

References (52)

1. DiMauro, S. and Schon, E.A. (2008) Mitochondrial disorders in the nervous system. Annu. Rev. Neurosci., 31, 91-123.
2. Wallace, D.C. (2010) Mitochondrial DNA mutations in disease and aging. Environ. Mol. Mutagen., 51, 440-450.
3. Wallace, D.C. (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet., 39, 359-407.
4. Wallace, D.C. (2012) Mitochondria and cancer. Nat. Rev. Cancer, 12, 685-698.
5. Kujoth, G.C., Hiona, A., Pugh, T.D., Someya, S., Panzer, K., Wohlgemuth, S.E., Hofer, T., Seo, A.Y., Sullivan, R., Jobling, W.A. et al. (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science, 309, 481-484.
6. Trifunovic,A.,Wredenberg,A., Falkenberg,M., Spelbrink, J.N.,Rovio,A.T., Bruder,C.E., Bohlooly,Y.M.,Gidlof, S., Oldfors, A.,Wibom,R. et al. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature, 429, 417-423.
7. Newman, N.J. (2002) From genotype to phenotype in Leber hereditary optic neuropathy: still more questions than answers. J. Neuroophthalmol., 22, 257-261.
8. Wallace, D.C., Singh,G., Lott,M.T.,Hodge, J.A., Schurr, T.G., Lezza,A.M., Elsas, L.J. 2nd and Nikoskelainen, E.K. (1988) Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science, 242, 1427-1430.
9. Singh, G., Lott, M.T. and Wallace, D.C. (1989) A mitochondrial DNA mutation as a cause of Leber's hereditary optic neuropathy. N. Engl. J. Med., 320, 1300-1305.
10. Adhya, S., Mahato, B., Jash, S., Koley, S., Dhar, G. and Chowdhury, T. (2011) Mitochondrial gene therapy: the tortuous path from bench to bedside. Mitochondrion, 11, 839-844.
11. Goldman, S.J., Taylor, R., Zhang, Y. and Jin, S. (2010) Autophagy and the degradation of mitochondria. Mitochondrion, 10, 309-315.
12. Lemasters, J.J. (2005) Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res., 8, 3-5.
13. Pan, T., Rawal, P., Wu, Y., Xie, W., Jankovic, J. and Le, W. (2009) Rapamycin protects against rotenone-induced apoptosis through autophagy induction. Neuroscience, 164, 541-551.
14. Sandoval, H., Thiagarajan, P., Dasgupta, S.K., Schumacher, A., Prchal, J.T., Chen, M. and Wang, J. (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature, 454, 232-235.
15. Narendra, D., Tanaka, A., Suen, D.F. and Youle, R.J. (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol., 183, 795-803.
16. Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y. et al. (2005) Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol., 169, 425-434.
17. Lee, I.H., Cao, L., Mostoslavsky, R., Lombard, D.B., Liu, J., Bruns, N.E., Tsokos, M., Alt, F.W. and Finkel, T. (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc. Natl Acad. Sci. USA, 105, 3374-3379.
18. Gilkerson, R.W., De Vries, R.L., Lebot, P., Wikstrom, J.D., Torgyekes, E., Shirihai, O.S., Przedborski, S. and Schon, E.A. (2012) Mitochondrial autophagy in cells with mtDNA mutations results from synergistic loss of transmembrane potential and mTORC1 inhibition. Hum. Mol. Genet., 21, 978-990.
19. Mahalati, K. and Kahan, B.D. (2001) Clinical pharmacokinetics of sirolimus. Clin. Pharmacokinet., 40, 573-585.
20. Twig, G., Elorza, A., Molina, A.J., Mohamed, H., Wikstrom, J.D., Walzer, G., Stiles, L., Haigh, S.E., Katz, S., Las, G. et al. (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J., 27, 433-446.
21. Kim, I., Rodriguez-Enriquez, S. and Lemasters, J.J. (2007) Selective degradation of mitochondria by mitophagy. Arch. Biochem. Biophys., 462, 245-253.
22. Suen, D.F., Narendra, D.P., Tanaka, A., Manfredi, G. and Youle, R.J. (2010) Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc. Natl Acad. Sci. USA, 107, 11835-11840.
23. Tanaka, M., Borgeld, H.J., Zhang, J.,Muramatsu, S., Gong, J.S., Yoneda, M., Maruyama, W., Naoi, M., Ibi, T., Sahashi, K. et al. (2002) Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J. Biomed. Sci., 9, 534-541.
24. de Vries, R.L., Gilkerson, R.W., Przedborski, S. and Schon, E.A. (2012) Mitophagy in cells with mtDNA mutations: being sick is not enough. Autophagy, 8, 699-700.
25. Geisler, S., Holmstrom, K.M., Skujat, D., Fiesel, F.C., Rothfuss, O.C., Kahle, P.J. and Springer, W. (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell. Biol., 12, 119-131.
26. Vives-Bauza,C.,Zhou, C.,Huang,Y.,Cui,M.,deVries,R.L.,Kim,J.,May, J., Tocilescu,M.A.,Liu,W.,Ko,H.S. etal. (2010) PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc. Natl Acad. Sci. USA, 107, 378-383.
27. Kraft, C., Peter, M. and Hofmann, K. (2010) Selective autophagy: ubiquitin-mediated recognition and beyond. Nat. Cell Biol., 12, 836-841.
28. Guertin, D.A. and Sabatini, D.M. (2007) Defining the role of mTOR in cancer. Cancer Cell, 12, 9-22.
29. Sarbassov, D.D., Ali, S.M., Sengupta, S., Sheen, J.H., Hsu, P.P., Bagley, A.F., Markhard, A.L. and Sabatini, D.M. (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell, 22, 159-168.
30. Lamming, D.W., Ye, L., Katajisto, P., Goncalves, M.D., Saitoh, M., Stevens, D.M., Davis, J.G., Salmon, A.B., Richardson, A., Ahima, R.S. et al. (2012) Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science, 335, 1638-1643.
31. Peterson, R.T. and Schreiber, S.L. (1998) Translation control: connecting mitogens and the ribosome. Curr. Biol., 8, R248-R250.
32. Jefferies, H.B., Fumagalli, S., Dennis, P.B., Reinhard, C., Pearson, R.B. and Thomas, G. (1997) Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k. EMBO J., 16, 3693-3704.
33. Huang, S. and Houghton, P.J. (2003) Targeting mTOR signaling for cancer therapy. Curr. Opin. Pharmacol., 3, 371-377.
34. Geoerger, B., Kerr, K., Tang, C.B., Fung, K.M., Powell, B., Sutton, L.N., Phillips, P.C. and Janss, A.J. (2001) Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/ medulloblastoma models as single agent and in combination chemotherapy. Cancer Res., 61, 1527-1532.
35. Tyler, B., Wadsworth, S., Recinos, V., Mehta, V., Vellimana, A., Li, K., Rosenblatt, J., Do, H., Gallia, G.L., Siu, I.M. et al. (2011) Local delivery of rapamycin: a toxicity and efficacy study in an experimental malignant glioma model in rats. Neurol. Oncol., 13, 700-709.
36. Newman, N.J. (1993) Leber's hereditary optic neuropathy. New genetic considerations. Arch. Neurol., 50, 540-548.
37. Bakker, A., Barthelemy, C., Frachon, P., Chateau, D., Sternberg, D., Mazat, J.P. and Lombes, A. (2000) Functional mitochondrial heterogeneity in heteroplasmic cells carrying the mitochondrial DNA mutation associated with the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes). Pediatr. Res., 48, 143-150.
38. Yano, T., Tanaka, M., Fukuda, N., Ueda, T. and Nagase, H. (2010) Loss of mutant mitochondrial DNA harboring the MELAS A3243G mutation in human cybrid cells after cell-cell fusion with normal tissue-derived fibroblast cells. Int. J. Mol. Med., 25, 153-158.
39. Sangatsuda, Y., Nakamura, M., Tomiyasu, A., Deguchi, A., Toyota, Y., Goto, Y., Nishino, I., Ueno, S. and Sano, A. (2012) Heteroplasmic m.1624C.T mutation of the mitochondrial tRNA(Val) gene in a proband and his mother with repeated consciousness disturbances. Mitochondrion, 12, 617-622.
40. Zhang, C., Liu, V.W., Addessi, C.L., Sheffield, D.A., Linnane, A.W. and Nagley, P. (1998) Differential occurrence of mutations in mitochondrial DNA of human skeletal muscle during aging. Hum. Mutat., 11, 360-371.
41. DiMauro, S. and Moraes, C.T. (1993) Mitochondrial encephalomyopathies. Arch. Neurol., 50, 1197-1208.
42. Rossignol, R., Malgat, M., Mazat, J.P. and Letellier, T. (1999) Threshold effect and tissue specificity. Implication for mitochondrial cytopathies. J. Biol. Chem., 274, 33426-33432.
43. Boulet, L., Karpati, G. and Shoubridge, E.A. (1992) Distribution and threshold expression of the tRNA(Lys) mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF). Am. J. Hum. Genet., 51, 1187-1200.
44. Simon, D.K. and Johns, D.R. (1999) Mitochondrial disorders: clinical and genetic features. Annu. Rev. Med., 50, 111-127.
45. Howell, N., Elson, J.L., Chinnery, P.F. and Turnbull, D.M. (2005) mtDNA mutations and common neurodegenerative disorders. Trends Genet., 21, 583-586.
46. Swerdlow, R.H., Parks, J.K., Miller, S.W., Tuttle, J.B., Trimmer, P.A., Sheehan, J.P., Bennett, J.P. Jr, Davis, R.E. and Parker, W.D.Jr. (1996) Origin and functional consequences of the complex I defect in Parkinson's disease. Ann. Neurol., 40, 663-671.
47. King, M.P. and Attardi, G. (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science, 246, 500-503.
48. Simon, D.K., Pulst, S.M., Sutton, J.P., Browne, S.E., Beal, M.F. and Johns, D.R. (1999) Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation. Neurology, 53, 1787-1793.
49. Dai, Y., Kiselak, T., Clark, J., Clore, E., Zheng, K., Cheng, A., Kujoth, G.C., Prolla, T.A., Maratos-Flier, E. and Simon, D.K. (2013) Behavioral and metabolic characterization of heterozygous and homozygousPOLGmutator mice. Mitochondrion, 13, 282-291.
50. Tashima, K., Zhang, S., Ragasa, R., Nakamura, E., Seo, J.H., Muvaffak, A. and Hagen, S.J. (2009) Hepatocyte growth factor regulates the development of highly pure cultured chief cells from rat stomach by stimulating chief cell proliferation in vitro. Am. J. Physiol. Gastrointest. Liver Physiol., 296, G319-G329.
51. Boland, B., Kumar, A., Lee, S., Platt, F.M., Wegiel, J., Yu, W.H. and Nixon, R.A. (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. J. Neurosci., 28, 6926-6937.
52. Chu, C.T. (2010) A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease. Hum. Mol. Genet., 19, R28-R37.