High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain
Abstract
The mitochondrial theory of aging proposes that mitochondrial DNA (mtDNA) accumulates mutations with age, and that these mutations contribute to physiological decline in aging and degenerative diseases. Although a great deal of indirect evidence supports this hypothesis, the aggregate burden of mtDNA mutations, particularly point mutations, has not been systematically quantified in aging or neurodegenerative disorders. Therefore, we directly assessed the aggregate burden of brain mtDNA point mutations in 17 subjects with Alzheimer's disease (AD), 10 elderly control subjects and 14 younger control subjects, using a PCR-cloning-sequencing strategy. We found that brain mtDNA from elderly subjects had a higher aggregate burden of mutations than brain mtDNA from younger subjects. The average aggregate mutational burden in elderly subjects was 2 x 10(-4) mutations/bp. The bulk of these mutations were individually rare point mutations, 60% of which changed an amino acid. Control experiments ensure that these results were not due to artifacts arising from PCR error, mistaken identification of nuclear pseudogenes or ex vivo oxidation. Cytochrome oxidase activity correlated negatively with increasing mutational burden. These findings significantly bolster the mitochondrial theory of aging.
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Age-related mtDNA changes occur within the human brain.
“Evidence indicates age-related mtDNA changes do in fact occur within the human brain.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [110]
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Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4526 · Cited by 341 · see citing works
RetractedMolecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
Sequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,640 · see citing works
Oxidants, antioxidants, and the degenerative diseases of aging.
Ames, B. N., Shigenaga, M. K., & Hagen, T. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7915 · Cited by 5,958 · see citing works
Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA
Andrews, R. M., Kubacka, I., Chinnery, P. F., Lightowlers, R. N., Turnbull, D. M., & Howell, N. (1999) · Nature Genetics · doi:10.1038/13779 · Cited by 3,337 · see citing works
Oxidative damage and mitochondrial decay in aging.
Shigenaga, M. K., Hagen, T. M., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10771 · Cited by 2,055 · see citing works
8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S., & Loeb, L. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48474-8 · Cited by 1,844 · see citing works
MITOCHONDRIAL DNA MUTATIONS AS AN IMPORTANT CONTRIBUTOR TO AGEING AND DEGENERATIVE DISEASES
Linnane, A. W., Ozawa, T., Marzuki, S., & Tanaka, M. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92145-4 · Cited by 1,192 · see citing works
Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease
Mecocci, P., MacGarvey, U., & Beal, M. F. (1994) · Annals of Neurology · doi:10.1002/ana.410360510 · Cited by 1,037 · see citing works
Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Flint Beal, M., & Wallace, D. C. (1992) · Nature Genetics · doi:10.1038/ng1292-324 · Cited by 890 · see citing works
Michikawa, Y., Mazzucchelli, F., Bresolin, N., Scarlato, G., & Attardi, G. M. (1999) · Science · doi:10.1126/science.286.5440.774 · Cited by 725 · see citing works
Helbock, H. J., Beckman, K. B., Shigenaga, M. K., Walter, P. B., Woodall, A., Yeo, H. C. H., & Ames, B. N. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.288 · Cited by 688 · see citing works
A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.
Cortopassi, G. A., Shibata, D. K., Soong, N.-W., & Arnheim, N. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7370 · Cited by 639 · see citing works
Brain cytochrome oxidase in Alzheimer's disease
Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09439.x · Cited by 537 · see citing works
Cortical Cytochrome Oxidase Activity Is Reduced in Alzheimer's Disease
Mutisya, E. M., Bowling, A. C., & Beal, M. F. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63062179.x · Cited by 531 · see citing works
Electron transport chain defects in Alzheimer's disease brain
Parker, W. D., Parks, J. K., Filley, C. M., & Kleinschmidt-DeMasters, B. K. (1994) · Neurology · doi:10.1212/wnl.44.6.1090 · Cited by 495 · see citing works
Mitochondrial DNA Variants Observed in Alzheimer Disease and Parkinson Disease Patients
Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. F., Mirra, S. S., Beal, M. F., Yang, C.-C., Gearing, M., Salvo, R., et al. (1993) · Genomics · doi:10.1006/geno.1993.1299 · Cited by 450 · see citing works
Ono, T., Isobe, K., Nakada, K., & Hayashi, J.-I. (2001) · Nature Genetics · doi:10.1038/90116 · Cited by 420 · see citing works
Mitochondria: a practical approach.
Darley-Usmar, V. M., RICKWOOD, D., & Wilson, M. T. (1987) · IRL Press eBooks · Cited by 410 · see citing works
A clinical overview of WT1 gene mutations
Little, M. H., & Wells, C. A. (1997) · Human Mutation · doi:10.1002/(sici)1098-1004(1997)9:3 · Cited by 392 · see citing works
Cooper, J. A. D., Mann, V. M., & Schapira, A. H. V. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90270-u · Cited by 335 · see citing works
Coller, H. A., Khrapko, K., Bodyak, N. D., Nekhaeva, E., Herrero-Jimenez, P., & Thilly, W. G. (2001) · Nature Genetics · doi:10.1038/88859 · Cited by 288 · see citing works
Cybrids in Alzheimer's disease: a cellular model of the disease?
Swerdlow, R. H., Parks, J. K., Cassarino, D. S., Maguire, D. J., Maguire, R. S., Bennett, J. P., Davis, R. E., & Parker, W. D. (1997) · Neurology · doi:10.1212/wnl.49.4.918 · Cited by 272 · see citing works
Age‐Dependent Impairment of Mitochondrial Function in Primate Brain
Bowling, A. C., Mutisya, E. M., Walker, L. C., Price, D. L., Cork, L. C., & Beal, M. H. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb13430.x · Cited by 263 · see citing works
Cybrids in Alzheimer's disease: A cellular model of the disease?
Swerdlow, R. H., & Parker, D. W. (1998) · Neurology · doi:10.1212/wnl.51.1.326-a · Cited by 260 · see citing works
Lee, H., Pang, C., Hsu, H., & Wei, Y. (1994) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(94)90056-6 · Cited by 255 · see citing works
Villani, G., Greco, M., Papa, S., & Attardi, G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.48.31829 · Cited by 225 · see citing works
Jones, J. B., Song, J. J., Hempen, P. M., Parmigiani, G., Hruban, R. H., & Kern, S. E. (2001) · PubMed · Cited by 219 · see citing works
Wallace, D. C., Stugard, C., Murdock, D. G., Schurr, T. G., & Brown, M. D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14900 · Cited by 219 · see citing works
Deleterious mitochondrial DNA mutations accumulate in aging human tissues
Arnheim, N., & Cortopassi, G. A. (1992) · Mutation Research/DNAging · doi:10.1016/0921-8734(92)90020-p · Cited by 215 · see citing works
Hamilton, M. L. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.10.2117 · Cited by 206 · see citing works
Aust, A. E., & Eveleigh, J. F. (1999) · Proceedings of the Society for Experimental Biology and Medicine · doi:10.1046/j.1525-1373.1999.d01-141.x · Cited by 191 · see citing works
Wang, L., Hirayasu, K., Ishizawa, M., & Kobayashi, Y. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.9.1774 · Cited by 186 · see citing works
Meltzer, C. C., Zubieta, J.-K., Brandt, J., Tune, L. E., Mayberg, H., & Frost, J. J. (1996) · Neurology · doi:10.1212/wnl.47.2.454 · Cited by 182 · see citing works
Mitochondrial mutational spectra in human cells and tissues
Khrapko, K., Coller, H. A., André, P. C., Li-Sucholeiki, X., Hanekamp, J. S., & Thilly, W. G. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13798 · Cited by 182 · see citing works
Bioenergetic consequences of accumulating the common 4977‐bp mitochondrial DNA deletion
Porteous, W. K., James, A. M., Sheard, P. W., Porteous, C. M., Packer, M. A., Hyslop, S. J., Melton, J. V., Pang, C., Wei, Y., & Murphy, M. P. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2570192.x · Cited by 159 · see citing works
Nakae, D., Mizumoto, Y., Kobayashi, E., Noguchi, O., & Konishi, Y. (1995) · Cancer Letters · doi:10.1016/0304-3835(95)03980-b · Cited by 158 · see citing works
Human brain contains high levels of heteroplasmy in the noncoding regions of mitochondrial DNA.
JAZIN, E. E., Cavelier, L. B., Eriksson, I., Oreland, L., & Gyllensten, U. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12382 · Cited by 144 · see citing works
Münscher, C., Rieger, T., Müller‐Höcker, J., & Kadenbach, B. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81484-h · Cited by 143 · see citing works
Lin, F. H., Lin, R. J., Wisniewski, H. M., Hwang, Y., Grundke, I., Healy-Louie, G., & Iqbal, K. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)80136-6 · Cited by 137 · see citing works
Hirano, M., Shtilbans, A., Mayeux, R. P., Davidson, M. M., DiMauro, S., Knowles, J. A., & Schon, E. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14894 · Cited by 133 · see citing works
Miller, S. W., Trimmer, P. A., Parker, W. D., & Davis, R. E. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67051897.x · Cited by 127 · see citing works
High levels of mitochondrial DNA deletions in skeletal muscle of old rhesus monkeys
Schwarze, S. R., Lee, C. M., Chung, S. S., Roecker, E. B., Weindruch, R. H., & Aiken, J. M. (1995) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(95)01611-3 · Cited by 121 · see citing works
Cortopassi, G. A., & Wang, E. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(95)00025-y · Cited by 121 · see citing works
Phenol sensitization of DNA to subsequent oxidative damage in 8-hydroxyguanine assays
Claycamp, H. G. (1992) · Carcinogenesis · doi:10.1093/carcin/13.7.1289 · Cited by 113 · see citing works
Diseases caused by nuclear genes affecting mtDNA stability
Suomalainen, A., & Kaukonen, J. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1379 · Cited by 109 · see citing works
Mitochondrial DNA haplogroups and susceptibility to AD and dementia with Lewy bodies
Chinnery, P. F., Taylor, G. A., Howell, N., Andrews, R. M., Morris, C. M., Taylor, R. W., McKeith, I. G., Perry, R. H., Edwardson, J. A., & Turnbull, D. M. (2000) · Neurology · doi:10.1212/wnl.55.2.302 · Cited by 102 · see citing works
N6-Furfuryladenine, Kinetin, Protects against Fenton Reaction-Mediated Oxidative Damage to DNA
Olsen, A., Siboska, G. E., Clark, B. F. C., & Rattan, S. I. S. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1669 · Cited by 100 · see citing works
Flux Control of Cytochrome c Oxidase in Human Skeletal Muscle
Kunz, W. S., Kudin, A. P., Vielhaber, S., Elger, C. E., Attardi, G. M., & Villani, G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004833200 · Cited by 96 · see citing works
Mitochondria. A practical approach
McCormack, J. (1988) · Biochemical Education · doi:10.1016/0307-4412(88)90107-0 · Cited by 95 · see citing works
Pallotti, F., Chen, X., Bonilla, E., & Schon, E. A. (1996) · PubMed Central · Cited by 93 · see citing works
Laderman, K., Penny, J. R., Mazzucchelli, F., Bresolin, N., Scarlato, G., & Attardi, G. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.27.15891 · Cited by 92 · see citing works
Association of the mitochondrial tRNAA4336G mutation with Alzheimer's and Parkinson's diseases
Egensperger, R., Kösel, S., Schnopp, N. M., Mehraein, P., & Graeber, M. B. (1997) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1997.tb01301.x · Cited by 90 · see citing works
Point Mutations of the mtDNA Control Region in Normal and Neurodegenerative Human Brains
Chinnery, P. F., Taylor, G. A., Howell, N., Brown, D. T., Parsons, T. J., & Turnbull, D. M. (2001) · The American Journal of Human Genetics · doi:10.1086/318204 · Cited by 88 · see citing works
Ito, S., Ohta, S., Nishimaki, K., Kagawa, Y., Soma, R., Kuno, S., Komatsuzaki, Y., Mizusawa, H., & Hayashi, J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2099 · Cited by 80 · see citing works
Accumulation of Deletions and Point Mutations in Mitochondrial Genome in Degenerative Diseases
TANAKA, M., KOVALENKO, S. A., Gong, J., Borgeld, H. W., Katsumata, K., Hayakawa, M., Yoneda, M., & Ozawa, T. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb39055.x · Cited by 69 · see citing works
Isobe, K., Ito, S., Hosaka, H., Iwamura, Y., Kondo, H., Kagawa, Y., & Hayashi, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.8.4601 · Cited by 59 · see citing works
The Frequency of Point Mutations in Mitochondrial DNA Is Elevated in the Alzheimer's Brain
Chang, S.-W., Zhang, D., Chung, H. D., & Zassenhaus, H. P. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2885 · Cited by 58 · see citing works
Is a point mutation in the mitochondrial ND2 gene associated with alzheimer's disease?
Petruzzella, V., Chen, X., & Schon, E. A. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)80834-4 · Cited by 54 · see citing works
Mitochondrial DNA Mutations in Alzheimer's Disease
Hutchin, T. P., Heath, P. R., Pearson, R. C. A., & Sinclair, A. J. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7793 · Cited by 51 · see citing works
Identification of cystic fibrosis mutations in the United Arab Emirates
Frossard, P. M., Girodon, E., Dawson, K. P., Ghanem, N., Plassa, F., Lestringant, G. G., & Goossens, M. (1998) · Human Mutation · doi:10.1002/(sici)1098-1004(1998)11:5 · Cited by 50 · see citing works
No association found between Alzheimer's disease and a mitochondrial tRNA glutamine gene variant
Wragg, M. A., Talbot, C. J., Morris, J. C., Lendon, C. L., & Goate, A. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)12146-3 · Cited by 44 · see citing works
Kösel, S., Egensperger, R., Mehraein, P., & Graeber, M. B. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2245 · Cited by 42 · see citing works
Kovalenko, S. A., Tanaka, M., Yoneda, M., Яковлев, А. Ф., & Ozawa, T. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0722 · Cited by 39 · see citing works
Davis, J. N., & Parker, W. D. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8353 · Cited by 35 · see citing works
Low Mutational Burden of Individual Acquired Mitochondrial DNA Mutations in Brain
Simon, D. K., Lin, M. T. S., Ahn, C., Liu, G.-J., Gibson, G. E., Beal, M. F., & Johns, D. R. (2001) · Genomics · doi:10.1006/geno.2001.6515 · Cited by 34 · see citing works
mtDNA Polymorphisms in Japanese Sporadic Alzheimer’s Disease
Tanno, Y., Okuizumi, K., & Tsuji, S. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00028-1 · Cited by 30 · see citing works
No mitochondrial haplotype was found to increase risk for alzheimer’s disease
Zsurka, G., Kalman, J. L., Juhász, A., Császár, A., Raskó, I., Janka, Z., & Venetianer, P. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00461-7 · Cited by 28 · see citing works
Tysoe, C. J., Robinson, D., Brayne, C., Dening, T., Paykel, E. S., Huppert, F. A., & Rubinsztein, D. C. (1996) · Journal of Medical Genetics · doi:10.1136/jmg.33.12.1002 · Cited by 27 · see citing works
Lin, F. H., & Lin, R. J. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)92332-r · Cited by 15 · see citing works
Flagged first, then by citations
1 of the 71 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Self-citationOxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357 · see citing works
Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: Recent advances.
Wang, W., Zhao, F., Ma, X., Perry, G., & Zhu, X. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00376-6 · Cited by 1,274 · see citing works
Detection of ultra-rare mutations by next-generation sequencing
Schmitt, M. W., Kennedy, S. R., Salk, J. J., Fox, E. J., Hiatt, J. B., & Loeb, L. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208715109 · Cited by 1,047 · see citing works
Reddy, P. H., & Beal, M. F. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.002 · Cited by 975 · see citing works
Mitochondria take center stage in aging and neurodegeneration
Beal, M. F. (2005) · Annals of Neurology · doi:10.1002/ana.20624 · Cited by 957 · see citing works
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
“Several investigators postulated somatic mtDNA mutations, accumulating over a person's lifespan, influence aging [33-35]; Wallace, in particular, championed the idea that somatic mtDNA mutations could cause AD [34].”
BackgroundA “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease
Swerdlow, R. H., & Khan, S. M. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.12.045 · Cited by 758 · see citing works
Yankner, B. A., Lu, T., & Loerch, P. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.2.010506.092044 · Cited by 677 · see citing works
Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging
Marchi, S., Giorgi, C., Suski, J. M., Agnoletto, C., Bononi, A., Bonora, M., Marchi, E. D., Missiroli, S., Patergnani, S., Poletti, F., et al. (2011) · Journal of Signal Transduction · doi:10.1155/2012/329635 · Cited by 639 · see citing works
Microglial cell dysregulation in brain aging and neurodegeneration
von Bernhardi, R., Eugenín-von Bernhardi, L., & Eugenín, J. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00124 · Cited by 556 · see citing works
The Alzheimer’s Disease Mitochondrial Cascade Hypothesis
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100339 · Cited by 562 · see citing works
“Young control, elderly control, and late-onset AD autopsy brains were evaluated for homoplasmic and heteroplasmic COX2 gene mutations [51].”
BackgroundCoskun, P. E., Beal, M. F., & Wallace, D. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403649101 · Cited by 556 · see citing works
Oxidative stress induces degradation of mitochondrial DNA
Shokolenko, I. N., Venediktova, N. I., Bochkareva, A., Wilson, G. L., & ALEXEYEV, M. F. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp100 · Cited by 556 · see citing works
Impaired Mitochondrial Biogenesis Contributes to Mitochondrial Dysfunction in Alzheimer's Disease
Sheng, B., Wang, X.-L., Su, B., Lee, H.-G., Casadesus, G., Perry, G., & Zhu, X.-W. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07581.x · Cited by 538 · see citing works
Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases
Giorgi, C., Marchi, S., Simões, I. C. M., Ren, Z., Morciano, G., Perrone, M., Patalas‐Krawczyk, P., Borchard, S., Jędrak, P., Pierzynowska, K., et al. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.05.006 · Cited by 467 · see citing works
Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease
Nissanka, N., & Moraes, C. T. (2017) · FEBS Letters · doi:10.1002/1873-3468.12956 · Cited by 453 · see citing works
Mańczak, M., Park, B. S., Jung, Y., & Reddy, P. H. (2004) · NeuroMolecular Medicine · doi:10.1385/nmm:5:2:147 · Cited by 432 · see citing works
Mitochondrial Diseases of the Brain
Chaturvedi, R. K., & Beal, M. F. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.018 · Cited by 416 · see citing works
Reddy, P. H., Tripathi, R., Troung, Q., Tirumala, K., Reddy, T. P., Anekonda, V., Shirendeb, U. P., Calkins, M. J., Reddy, A. P., Mao, P., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.011 · Cited by 394 · see citing works
Monzio Compagnoni, G., Di Fonzo, A., Corti, S., Comi, G. P., Bresolin, N., & Masliah, E. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01926-1 · Cited by 378 · see citing works
Kennedy, S. R., Salk, J. J., Schmitt, M. W., & Loeb, L. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003794 · Cited by 363 · see citing works
Reddy, P. H. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03530.x · Cited by 356 · see citing works
Mitochondrial DNA repair and aging
Mandavilli, B. S., Santos, J. H., & Houten, B. V. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(02)00220-8 · Cited by 338 · see citing works
Mitochondrial dysfunction in aging: Much progress but many unresolved questions
Payne, B. A. I., & Chinnery, P. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.022 · Cited by 335 · see citing works
Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease
Eckert, A., Keil, U., Marques, C. A., Bonert, A., Frey, C., Schüssel, K., & Müller, W. E. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00534-3 · Cited by 309 · see citing works
Brain aging, Alzheimer's disease, and mitochondria
Swerdlow, R. H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.08.012 · Cited by 306 · see citing works
“Another study catalogued low abundance heteroplasmic mutations in COX1, a COX subunit gene located on the mtDNA [110].”
BackgroundMitochondrial Approaches for Neuroprotection
Chaturvedi, R. K., & Beal, M. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.027 · Cited by 294 · see citing works
Are mitochondria critical in the pathogenesis of Alzheimer's disease?
Reddy, P. H., & Beal, M. F. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.03.004 · Cited by 289 · see citing works
Mitochondrial Aspects of Synaptic Dysfunction in Alzheimer’s Disease
Cai, Q., & Tammineni, P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160726 · Cited by 274 · see citing works
Mitophagy in Alzheimer’s Disease and Other Age-Related Neurodegenerative Diseases
Cai, Q., & Jeong, Y. Y. (2020) · Cells · doi:10.3390/cells9010150 · Cited by 263 · see citing works
Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease
Reddy, P. H. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.03.042 · Cited by 264 · see citing works
Mitochondrial Dysfunction and Glaucoma
Kong, G. Y. X., Bergen, N. J. V., Trounce, I. A., & Crowston, J. G. (2009) · Journal of Glaucoma · doi:10.1097/ijg.0b013e318181284f · Cited by 261 · see citing works
Fukui, H., & Moraes, C. T. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.008 · Cited by 248 · see citing works
Molecular aging in human prefrontal cortex is selective and continuous throughout adult life
Erraji-Benchekroun, L., Underwood, M. D., Arango, V., Galfalvy, H., Pavlidis, P., Smyrniotopoulos, P., Mann, J. J., & Sibille, E. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.034 · Cited by 236 · see citing works
Reddy, P. H., Mańczak, M., Mao, P., Calkins, M. J., Reddy, A. P., & Shirendeb, U. P. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100504 · Cited by 240 · see citing works
Coble, M. D., Just, R. S., O’Callaghan, J. E., Letmanyi, I. H., Peterson, C. T., Irwin, J. A., & Parsons, T. J. (2004) · International Journal of Legal Medicine · doi:10.1007/s00414-004-0427-6 · Cited by 238 · see citing works
Pathogenesis of Alzheimer's disease.
Swerdlow, R. H. (2007) · PubMed Central · Cited by 236 · see citing works
Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update
Cenini, G., & Voos, W. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00902 · Cited by 257 · see citing works
Barja, G. (2004) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1017/s1464793103006213 · Cited by 232 · see citing works
Oxidative stress and the mitochondrial theory of aging in human skeletal muscle
Parise, G., Jan, K. J., Douglas, M. J., Phillips, S. M., & Tarnopolsky, M. A. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.06.002 · Cited by 223 · see citing works
Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases
Reddy, P. H., & Reddy, T. P. (2011) · Current Alzheimer Research · doi:10.2174/156720511795745401 · Cited by 227 · see citing works
Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation
Wong, W. T. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00022 · Cited by 227 · see citing works
Toxicity of Amyloid β Peptide: Tales of Calcium, Mitochondria, and Oxidative Stress
Canevari, L., Abramov, A. Y., & Duchen, M. R. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000014834.06405.af · Cited by 221 · see citing works
Mitochondrial Variants in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder
Rollins, B. L., Martin, M. V., Sequeira, A., Moon, E. A., Morgan, L. Z., Watson, S. J., Schatzberg, A. F., Akil, H., Myers, R., Jones, E. G., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004913 · Cited by 212 · see citing works
The Alzheimer's disease mitochondrial cascade hypothesis: an update
Swerdlow, R. H., & Khan, S. M. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.01.011 · Cited by 206 · see citing works
Swerdlow, R. H. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4149 · Cited by 203 · see citing works
Regulation of neuron mitochondrial biogenesis and relevance to brain health
Onyango, I. G., Lu, J., Rodova, M., Lezi, E., Crafter, A. B., & Swerdlow, R. H. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.07.014 · Cited by 188 · see citing works
Mitochondrial Dysfunction in Aging and Alzheimer's Disease: Strategies to Protect Neurons
Reddy, P. H. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1754 · Cited by 187 · see citing works
The Role of Mitochondrial DNA Mutations in Mammalian Aging
Kujoth, G. C., Bradshaw, P. C., Haroon, S., & Prolla, T. A. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030024 · Cited by 186 · see citing works
Reddy, P. H. (2009) · CNS Spectrums · doi:10.1017/s1092852900024901 · Cited by 186 · see citing works
Mechanisms linking mtDNA damage and aging
Pinto, M., & Moraes, C. T. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.05.005 · Cited by 179 · see citing works
DeBalsi, K. L., Hoff, K. E., & Copeland, W. C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.006 · Cited by 180 · see citing works
The role of mitochondria in inherited neurodegenerative diseases
Kwong, J. Q., Beal, M. F., & Manfredi, G. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03990.x · Cited by 180 · see citing works
Hayashi, Y., Yoshida, M., Yamato, M., Ide, T., Wu, Z., Ochi-Shindou, M., Kanki, T., Kang, D., Sunagawa, K., Tsutsui, H., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1957-08.2008 · Cited by 180 · see citing works
He, Z., Zou, S., Li, M., Liao, F.-L., Wu, X., Sun, H., Zhao, X., Hu, Y., Li, D., Xu, X., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101364 · Cited by 170 · see citing works
Santos, A. L., Sinha, S., & Lindner, A. B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1941285 · Cited by 168 · see citing works
Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas
Área-Gómez, E., Guardia‐Laguarta, C., Schon, E. A., & Przedborski, S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci120848 · Cited by 169 · see citing works
Morton, H., Kshirsagar, S., Orlov, E., Bunquin, L. E., Sawant, N. A., Boleng, L., George, M., Basu, T., Ramasubramanian, B., Pradeepkiran, J. A., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.07.013 · Cited by 171 · see citing works
The mitochondrial free radical theory of ageing - Where do we stand?
Gruber, J. (2008) · Frontiers in bioscience · doi:10.2741/3174 · Cited by 168 · see citing works
Mitochondrial DNA mutations in neurodegeneration
Keogh, M. J., & Chinnery, P. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.015 · Cited by 163 · see citing works
The role of mitophagy in the regulation of mitochondrial energetic status in neurons
Han, S., Zhang, M., Jeong, Y. Y., Margolis, D. J., & Cai, Q. (2021) · Autophagy · doi:10.1080/15548627.2021.1907167 · Cited by 151 · see citing works
Nakanishi, H., & Wu, Z. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.02.001 · Cited by 149 · see citing works
Mitoenergetic failure in Alzheimer disease
Parihar, M. S., & Brewer, G. J. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00232.2006 · Cited by 149 · see citing works
Cytoplasmic hybrid (cybrid) cell lines as a practical model for mitochondriopathies
Wilkins, H., Carl, S. M., & Swerdlow, R. H. (2014) · Redox Biology · doi:10.1016/j.redox.2014.03.006 · Cited by 152 · see citing works
Devi, L., & Anandatheerthavarada, H. K. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.07.007 · Cited by 150 · see citing works
ALEXEYEV, M. F., LeDoux, S. P., & Wilson, G. L. (2004) · Clinical Science · doi:10.1042/cs20040148 · Cited by 149 · see citing works
Jones, A. W. E., Yao, Z., Vicencio, J. M., Karkucińska‐Więckowska, A., & Szabadkai, G. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.09.009 · Cited by 145 · see citing works
Mitochondrial DNA Mutations in Disease, Aging, and Neurodegeneration
Reeve, A. K., Krishnan, K. J., & Turnbull, D. M. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.016 · Cited by 146 · see citing works
Eckert, A., Keil, U., Scherping, I., Hauptmann, S., & MÜLLER, W. E. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1352.023 · Cited by 145 · see citing works
Multiple faces of dynamin-related protein 1 and its role in Alzheimer's disease pathogenesis
Kandimalla, R. J. L., & Reddy, P. H. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.018 · Cited by 144 · see citing works
Reddy, P. H. (2011) · Pharmaceuticals · doi:10.3390/ph4030429 · Cited by 143 · see citing works
Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation
Yang, L., Youngblood, H. A., Wu, C., & Zhang, Q. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00197-z · Cited by 143 · see citing works
High frequency of mitochondrial complex I mutations in Parkinson’s disease and aging
Smigrodzki, R. M., Parks, J. K., & Parker, W. D. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.020 · Cited by 138 · see citing works
Mastroeni, D., Khdour, O. M., Delvaux, E., Nolz, J., Olsen, G., Berchtold, N. C., Cotman, C. W., Hecht, S. M., & Coleman, P. D. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.09.003 · Cited by 131 · see citing works
Effects of EGb 761® Ginkgo biloba Extract on Mitochondrial Function and Oxidative Stress
Eckert, A., Keil, U., Kressmann, S., Schindowski, K., Leutner, S., Leutz, S., & Müller, W. E. G. (2003) · Pharmacopsychiatry · doi:10.1055/s-2003-40449 · Cited by 132 · see citing works
Briston, T., & Hicks, A. R. (2018) · Biochemical Society Transactions · doi:10.1042/bst20180025 · Cited by 129 · see citing works
Mitochondria in cybrids containing mtDNA from persons with mitochondriopathies
Swerdlow, R. H. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21167 · Cited by 128 · see citing works
Mitochondria in Alzheimer's disease
Swerdlow, R. H., & Kish, S. J. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)53013-0 · Cited by 126 · see citing works
Mitochondrial dysfunction and Alzheimer's disease
Maruszak, A., & Żekanowski, C. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.07.004 · Cited by 123 · see citing works
Somatic mitochondrial DNA mutations in early parkinson and incidental lewy body disease
Lin, M. T. S., Cantuti‐Castelvetri, I., Zheng, K., Jackson, K. E., Tan, Y. B., Arzberger, T., Lees, A. J., Betensky, R. A., Beal, M. F., & Simon, D. K. (2012) · Annals of Neurology · doi:10.1002/ana.23568 · Cited by 125 · see citing works
Accumulation of point mutations in mitochondrial DNA of aging mice
Khaidakov, M., Heflich, R. H., Manjanatha, M. G., Myers, M. B., & Aidoo, A. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(03)00010-1 · Cited by 123 · see citing works
The Mitochondrial and Autosomal Mutation Landscapes of Prostate Cancer
Lindberg, J., Mills, I. G., Klevebring, D., Liu, W., Neiman, M., Xu, J., Wikström, P., Wiklund, P. N., Wiklund, F. E., Egevad, L., et al. (2012) · European Urology · doi:10.1016/j.eururo.2012.11.053 · Cited by 117 · see citing works
Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson’s disease
Simon, D. K., Lin, M. T., Zheng, L., Liu, G.-J., Ahn, C. H., Kim, L. M., Mauck, W. M., Twu, F., Beal, M. F., & Johns, D. R. (2004) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00037-x · Cited by 118 · see citing works
Self-citationNew Insights in the Amyloid-Beta Interaction with Mitochondria
Spuch, C., Ortolano, S., & Fernández-Balbuena, C. N. (2012) · Journal of Aging Research · doi:10.1155/2012/324968 · Cited by 117 · see citing works
The mitochondrial theory of aging: dead or alive?
Jacobs, H. T. (2003) · Aging Cell · doi:10.1046/j.1474-9728.2003.00032.x · Cited by 117 · see citing works
Reddy, P. H., Manczak, M., & Yin, X. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170051 · Cited by 116 · see citing works
Klein, H., Trumpff, C., Yang, H., Lee, A., Picard, M. A., Bennett, D. A., & Jager, P. L. D. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00495-8 · Cited by 110 · see citing works
Trifunović, A. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.03.003 · Cited by 110 · see citing works
Pharmacogenomics in Alzheimer's Disease
Cacabelos, R. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-205-2_10 · Cited by 109 · see citing works
Mitochondria, Cybrids, Aging, and Alzheimer's Disease
Swerdlow, R. H., Koppel, S., Weidling, I., Hayley, C., Ji, Y., & Wilkins, H. M. (2017) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2016.12.017 · Cited by 106 · see citing works
Zádori, D., Veres, G., Szalárdy, L., Klivènyi, P., & Vécsei, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170929 · Cited by 107 · see citing works
Bernardo, T. C., Marques‐Aleixo, I., Beleza, J., Oliveira, P. J., Ascensão, A., & Magalhães, J. (2016) · Brain Pathology · doi:10.1111/bpa.12403 · Cited by 108 · see citing works
Cause or casualty: The role of mitochondrial DNA in aging and age-associated disease
Chocrón, E. S., Munkácsy, E., & Pickering, A. M. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.09.035 · Cited by 106 · see citing works
Neurological disorders and mitochondria
Cabral‐Costa, J. V., & Kowaltowski, A. J. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.10.003 · Cited by 100 · see citing works
Mullane, K., & Williams, M. J. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113945 · Cited by 106 · see citing works
Hoekstra, J. G., Hipp, M. J., Montine, T. J., & Kennedy, S. R. (2016) · Annals of Neurology · doi:10.1002/ana.24709 · Cited by 105 · see citing works
Understanding aging: revealing order out of chaos
Dufour, É., & Larsson, N. (2004) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2004.04.020 · Cited by 101 · see citing works
The complex crosstalk between mitochondria and the nucleus: What goes in between?
Cagin, U., & Enrı́quez, J. A. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.01.026 · Cited by 101 · see citing works
Does the mitochondrial genome play a role in the etiology of Alzheimer’s disease?
Elson, J. L., Herrnstadt, C., Preston, G., Thal, L. J., Morris, C. M., Edwardson, J. A., Beal, M. F., Turnbull, D. M., & Howell, N. (2006) · Human Genetics · doi:10.1007/s00439-005-0123-8 · Cited by 100 · see citing works
- Authors
- Lin, M. T.
- Affiliations
- Cornell University (US)
- Corresponding author
- Lin, M. T.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-01-01
- Volume
- 11
- Issue
- 2
- Pages
- 133-145
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2148641357
- Cited by
- 366
- References
- 71
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 12 · 2022: 17 · 2021: 19 · 2020: 15 · 2019: 13 · 2018: 21 · 2017: 8 · 2016: 20 · 2015: 15 · 2014: 11 · 2013: 13 · 2012: 20
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ns001971-03, 5k08ag000798-03)
- National Institute on Aging (K08-AG00798)
- National Institute of Neurological Disorders and Stroke (K08 NS01971)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- mitochondrial DNA, somatic mtDNA mutations, point mutations, aging, Alzheimer's disease, mitochondrial theory of aging, brain, cytochrome oxidase activity, neurodegeneration
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Child, Cloning, Molecular, Electron Transport Complex IV, DNA, Mitochondrial, Female, Humans, Infant, Male, Middle Aged, Molecular Sequence Data, Pseudogenes, Polymerase Chain Reaction, Point Mutation, Sequence Analysis, DNA
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