A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine

Annual Review of Genetics - Tập 39 Số 1 - Trang 359-407 - 2005
Douglas C. Wallace1
1Center for Molecular and Mitochondrial Medicine and Genetics, Departments of Ecology and Evolutionary Biology, Biological Chemistry, and Pediatrics, University of California, Irvine, California 92697-3940;

Tóm tắt

Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.

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Tài liệu tham khảo

10.1016/S0092-8674(04)00452-0

Adams JU, 2005, How keeping house may keep one young. Scientist, 19, 22

10.1016/0885-4505(91)90032-G

10.1002/elps.1150180504

10.1038/79839

Alzheimer's Association. 2005. Alzheimer's Disease Statistics. http://www.alz.org/Resources/FactSheets/FSAlzheimerStats.pdf

Anandatheerthavarada HK, 2003, J. Biol. Chem., 161, 41

10.1002/1531-8249(199901)45:1<127::AID-ART20>3.0.CO;2-Y

10.1016/S0006-291X(02)00735-0

10.1016/j.semcancer.2003.09.013

10.1086/321282

10.1002/(SICI)1097-0045(19970901)32:4<229::AID-PROS1>3.0.CO;2-E

10.1038/ng0894-458

10.1038/ng0492-11

10.1126/science.287.5454.848

10.1126/science.1078223

10.1016/S0197-4580(01)00314-1

10.1002/1097-0142(20000701)89:1<123::AID-CNCR17>3.0.CO;2-9

10.1038/ng1095-144

10.1007/s00439-001-0660-8

10.1086/515488

10.1074/jbc.M006476200

10.1007/s004390100538

10.1126/science.1094637

10.1086/302546

10.1073/pnas.71.5.1681

10.1016/S0014-5793(99)01028-5

10.1038/325031a0

10.1016/S0197-4580(03)00033-2

10.1002/jnr.10389

Cent. Dis. Control Prev. 2005. Prostate Cancer: The Public Health Perspective, 2004/2005 Fact Sheet. http://www.cdc.gov/cancer/prostate/prospdf/about2004.pdf

10.1002/(SICI)1096-8628(19990702)85:1<20::AID-AJMG6>3.0.CO;2-K

Chen JZ, 2002, Cancer Res., 62, 6470

10.1016/S0140-6736(02)11310-9

10.1126/science.1069366

10.1126/science.1057991

10.1002/ana.410430119

10.1081/CNV-120002155

10.1038/ng1292-324

10.1006/geno.1994.1525

10.1016/0921-8734(92)90021-G

Corral-Debrinski M, 1991, Implications for cardiac disease. JAMA, 266, 1812

10.1093/nar/18.23.6927

10.1073/pnas.0630589100

10.1046/j.1365-2990.2002.00414.x

10.1523/JNEUROSCI.4276-04.2005

10.1073/pnas.0337639100

10.2337/diabetes.52.3.642

10.1016/0006-291X(89)92702-2

10.1096/fasebj.13.12.1532

10.1056/NEJMra022567

10.1006/mcpr.1996.0053

10.1007/s001250100032

10.1073/pnas.96.9.4820

10.1016/S0921-8777(00)00046-X

10.1016/S1534-5807(01)00071-5

10.1046/j.1471-4159.2002.00812.x

10.1126/science.287.5460.2017

10.1042/BJ20030022

10.1073/pnas.89.1.202

10.1016/j.tcb.2004.07.006

10.2741/gibson

10.1073/pnas.77.11.6715

10.1038/348651a0

10.1038/35041700

10.1002/(SICI)1097-0215(19991126)83:5<625::AID-IJC10>3.0.CO;2-N

10.1073/pnas.171202698

10.1074/jbc.M404500200

10.1093/jn/117.2.376

10.1001/archneur.60.8.1119

10.1016/S0168-9525(01)02523-9

10.1002/pmic.200300461

10.2337/diacare.26.3.917

10.1038/331717a0

Holt IJ, 1990, Am. J. Hum. Genet., 46, 428

10.1212/WNL.45.10.1879

10.1002/(SICI)1098-2264(199602)15:2<95::AID-GCC3>3.0.CO;2-Z

10.1016/j.cell.2004.09.016

10.1016/S0002-9440(10)64553-1

10.1021/bi990438f

10.1073/pnas.92.15.6892

10.1038/35001622

10.1038/35047064

10.1038/29331

Jaarsma D, 2001, Acta Neuropathol., 102, 293, 10.1007/s004010100399

10.1007/BF02099973

10.1073/pnas.021337498

10.1073/pnas.91.13.6206

10.1073/pnas.2135217100

Kelley MR, 2001, Clin. Cancer Res., 7, 824

10.1089/15230860152543014

10.1101/gad.1177604

10.1126/science.277.5328.942

10.1126/science.2814477

10.1002/(SICI)1098-2264(199909)26:1<80::AID-GCC11>3.0.CO;2-4

10.1046/j.1471-4159.1999.0720700.x

10.1073/pnas.051627098

10.1038/nature02229

10.1016/S0891-5849(01)00688-8

10.1016/j.brainresrev.2004.05.001

10.1016/S0891-5849(00)00458-5

10.1016/S0092-8674(00)80701-1

10.1038/ng0897-345

10.1093/emboj/21.10.2383

10.1210/en.2003-0288

10.1126/science.285.5432.1390

10.1038/77046

10.1074/jbc.M105326200

10.1126/science.1083614

10.1038/ng1056

10.1172/JCI10268

10.1016/S0002-9440(10)63091-X

10.1042/BJ20041081

Lemieux J, 2001, Genetics, 159, 147, 10.1093/genetics/159.1.147

10.1038/ng1295-376

10.1038/45257

10.1038/nature00904

10.1016/j.cell.2004.09.013

10.1101/gad.1164804

10.1016/S0955-0674(03)00006-1

10.1074/jbc.M205087200

10.1016/S0960-9822(02)01146-6

10.1016/S0092-8674(01)00524-4

10.1126/science.1091230

10.1016/0885-4505(88)90061-8

10.1111/j.1532-5415.1993.tb06767.x

10.1093/geronj/47.6.B202

10.1093/hmg/ddh103

10.1016/S0002-9440(10)61132-7

McCarter RJ, 1992, Am. J. Physiol., 263, E448

McCord JM, 2000, Am. J. Med. Genet., 108, 652

10.1177/003335490411900211

10.1176/appi.ajp.157.7.1058

10.1002/ana.410360510

10.1002/ana.410340416

Melendez A, 2003, elegans. Science, 301, 1387

10.1073/pnas.96.3.846

10.1523/JNEUROSCI.21-21-08348.2001

10.1093/nar/25.5.974

10.1126/science.289.5484.1567

10.1016/S0197-4580(99)00092-5

10.1038/ng0298-159

10.1093/nar/23.20.4122

10.1007/BF02102807

10.1126/science.286.5440.774

10.1038/46311

10.1002/humu.10304

10.1073/pnas.0136972100

MITOMAP. 2005. A Human Mitochondrial Genome Database. http://www.mitomap.org

10.1074/jbc.C000889200

10.1038/ng0996-55

10.1073/pnas.0401401101

10.1038/ng1180

10.1056/NEJM198905183202001

10.1016/S0092-8674(04)00126-6

10.2337/diabetes.52.3.895

10.1093/nar/28.21.4350

10.1046/j.1471-4159.1994.63062179.x

10.1007/s004010050997

Natl. Parkinson Found. 2004. About Parkinson Disease. http://www.parkinson.org/site/pp.asp?c=9dJFJLPwB&b=71125

10.1074/jbc.M501485200

10.1038/81551

10.1007/s00439-002-0843-y

10.1016/S1471-1931(00)00031-8

10.1038/40194

10.1074/jbc.M105395200

10.1073/pnas.132260399

10.1126/science.8108730

10.1074/jbc.M401844200

10.1016/S0304-3940(03)00941-8

10.1074/jbc.M401135200

10.1038/nn884

10.1038/534

Patrick L, 2002, Alt. Med. Rev., 7, 276

10.1073/pnas.1032913100

10.1056/NEJMoa031314

10.1073/pnas.0408894102

10.1038/sj.ijo.0802912

10.1038/nature02583

10.1016/S0960-9822(02)00808-4

10.1038/3108

10.1126/science.276.5321.2045

10.1016/S0006-2952(01)00919-4

10.1016/S0092-8674(00)81410-5

10.1006/nbdi.1999.0273

10.1016/S0169-328X(00)00268-0

10.1038/nature03354

10.1126/science.290.5499.2137

10.1038/sj.ejhg.5200703

10.1111/j.1749-6632.1996.tb34413.x

10.1016/S0531-5565(01)00094-8

10.1038/ng1097-215

Ruiz-Pesini E, 1998, Clin. Chem., 44, 1616, 10.1093/clinchem/44.8.1616

10.1126/science.1088434

10.1038/13518

10.1016/S0167-4781(02)00343-3

Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, et al. 2005. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–11

10.1074/jbc.M104718200

10.1006/geno.1993.1299

10.1016/0092-8674(90)90059-N

10.1038/81649

10.1212/WNL.53.8.1787

10.1016/S0891-5849(02)01021-3

10.1016/0047-6374(94)90104-X

10.1002/ana.10682

10.1038/ng1292-318

Sturtz LA, 2001, J. Biol. Chem., 276, 38084, 10.1074/jbc.M105296200

Sun J, 2002, Genetics, 161, 661, 10.1093/genetics/161.2.661

Tan DJ, 2002, Cancer Res., 62, 972

10.1016/S0047-6374(00)00149-4

10.1016/S0140-6736(05)78211-8

10.1097/00019052-200008000-00003

Tatuch Y, 1992, Am. J. Hum. Genet., 50, 852

10.1038/35065638

10.1016/S1534-5807(01)00098-3

10.1038/nature02517

10.1016/j.nbd.2003.09.011

10.1038/sj.onc.1205513

10.1073/pnas.91.18.8334

10.1016/S0076-6879(96)64044-0

10.1126/science.1096284

10.1523/JNEUROSCI.21-13-04923.2001

10.2337/diabetes.43.6.746

10.1016/j.neulet.2004.04.051

10.1086/373937

10.1152/physiolgenomics.00122.2003

10.1086/381054

10.1046/j.1469-1809.2001.6520111.x

10.1016/S0092-8674(01)00527-X

10.1128/MCB.20.5.1868-1876.2000

10.1530/eje.0.1380233

10.1006/exnr.2000.7385

Wallace DC, 1982, Microbiol. Rev., 46, 208, 10.1128/mr.46.2.208-240.1982

10.1146/annurev.bi.61.070192.005523

10.1126/science.1533953

Wallace DC, 1997, The Molecular and Genetic Basis of Neurological Disease, 237

10.1126/science.283.5407.1482

10.1002/ajmg.1393

10.1016/S0378-1119(99)00295-4

10.1083/jcb.67.1.174

Wallace DC, Lott MT. 2002. Mitochondrial genes in degenerative diseases, cancer and aging. InEmery and Rimoin's Principles and Practice of Medical Genetics, ed.DL Rimoin, JM Connor, RE Pyeritz, BR Korf, pp.299–409. London: Churchill Livingstone

Wallace DC, Lott MT, Brown MD, Kerstann K. 2001. Mitochondria and neuro-ophthalmological diseases. InThe Metabolic and Molecular Basis of Inherited Disease, ed.CR Scriver, AL Beaudet, WS Sly, D Valle, pp.2425–512. New York: McGraw-Hill

10.1126/science.3201231

10.1016/0092-8674(88)90218-8

10.1073/pnas.061013598

Warburg O. 1931. The Metabolism of Tumors. New York: R.R. Smith

10.1016/S0169-328X(01)00029-8

10.1126/science.1102521

10.1038/ng0897-352

10.1007/s001250050044

10.1016/S0092-8674(00)80611-X

10.1038/sj.onc.1202265

10.1038/sj.onc.1203537

10.1038/35093050

10.1016/S1534-5807(03)00170-9

10.1073/pnas.242719399

10.1038/414782a

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Annual Review of Genetics

Tập 39 Số 1

359-407

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