Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function

被引:207
|
作者
Wei, YH [1 ]
Lu, CY
Lee, HC
Pang, CY
Ma, YS
机构
[1] Natl Yang Ming Univ, Sch Life Sci, Dept Biochem, Taipei 112, Taiwan
[2] Natl Yang Ming Univ, Sch Life Sci, Ctr Cellular & Mol Biol, Taipei 112, Taiwan
来源
TOWARDS PROLONGATION OF THE HEALTHY LIFE SPAN: PRACTICAL APPROACHES TO INTERVENTION | 1998年 / 854卷
关键词
D O I
10.1111/j.1749-6632.1998.tb09899.x
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Mitochondrial respiration and oxidative phosphorylation are gradually uncoupled, and the activities of the respiratory enzymes are concomitantly decreased in various human tissues upon aging, An immediate consequence of such gradual impairment of the respiratory function is the increase in the production of the reactive oxygen species (ROS) and free radicals in the mitochondria through the increased electron leak of the electron transport chain, Moreover, the intracellular levels of antioxidants and free radical scavenging enzymes are gradually altered. These two compounding factors lead to an age-dependent increase in the fraction of the ROS and free radical that may escape the defense mechanism and cause oxidative damage to various biomolecules in tissue cells. A growing body of evidence has established that the levels of ROS and oxidative damage to lipids, proteins, and nucleic acids are significantly increased with age in animal and human tissues. The mitochondrial DNA (mtDNA), although not protected by histones or DNA-binding proteins, is susceptible to oxidative damage by the ever-increasing levels of ROS and free radicals in the mitochondrial matrix. In the past few Sears, oxidative modification (formation of 8-hydroxy-2'-deoxyguanosine) and large-scale deletion and point mutation of mtDNA have been found to increase exponentially with age in various human tissues, The respiratory enzymes containing the mutant mtDNA-encoded defective protein subunits inevitably exhibit impaired respiratory function and thereby increase electron leak and ROS production, which in turn elevates the oxidative stress and oxidative damage of the mitochondria, This vicious cycle operates in different tissue cells at different rates and thereby leads to the differential accumulation of mutation and oxidative damage to mtDNA in human aging, This may also play some role in the pathogenesis of degenerative diseases and the age-dependent progression of the clinical course of mitochondrial diseases.
引用
收藏
页码:155 / 170
页数:16
相关论文
共 50 条
  • [41] Mitochondrial oxidative stress results in a decline of mitochondrial function and increased apoptosis with age in the Sod2+/- mouse.
    Kokoszka, JE
    Coskun, P
    Levy, SE
    Esposito, LE
    Wallace, DC
    AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (04) : 293 - 293
  • [42] AGE-DEPENDENT CHANGES IN THE EXPRESSION OF DROSOPHILA MITOCHONDRIAL PROTEINS
    FLEMING, JE
    MELNIKOFF, PS
    LATTER, GI
    CHANDRA, D
    BENSCH, KG
    MECHANISMS OF AGEING AND DEVELOPMENT, 1986, 34 (01) : 63 - 72
  • [43] Age-Dependent Decline in Synaptic Mitochondrial Function Is Exacerbated in Vulnerable Brain Regions of Female 3xTg-AD Mice
    Espino de la Fuente-Munoz, Cesar
    Rosas-Lemus, Monica
    Moreno-Castilla, Perla
    Bermudez-Rattoni, Federico
    Uribe-Carvajal, Salvador
    Arias, Clorinda
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (22) : 1 - 13
  • [44] Role of Mitochondrial Complex IV in Age-Dependent Obesity
    Soro-Arnaiz, Ines
    Yang Li, Qilong Oscar
    Torres-Capelli, Mar
    Melendez-Rodriguez, Florinda
    Veiga, Sonia
    Veys, Koen
    Sebastian, David
    Elorza, Ainara
    Tello, Daniel
    Hernansanz-Agustin, Pablo
    Cogliati, Sara
    Maria Moreno-Navarrete, Jose
    Balsa, Eduardo
    Fuertes, Esther
    Romanos, Eduardo
    Martinez-Ruiz, Antonio
    Antonio Enriquez, Jose
    Manuel Fernandez-Real, Jose
    Zorzano, Antonio
    De Bock, Katrien
    Aragones, Julian
    CELL REPORTS, 2016, 16 (11): : 2991 - 3002
  • [45] Role of lipoperoxidation on oxidative damage to mitochondrial respiratory chain
    Cortes-Rojo, Christian
    Estrada-Villagomez, Mirella
    Corona-Gomez, Rosalia
    Calderon-Cortes, Elizabeth
    Clemente-Guerrero, Monica
    Esquivel-Gutierrez, Edgar
    Caudillo-Noriega, Evangelina
    Noriega-Cisneros, Ruth
    Manzo-Avalos, Salvador
    FASEB JOURNAL, 2007, 21 (05): : A662 - A662
  • [46] AGE-DEPENDENT 6KB DELETION IN HUMAN LIVER MITOCHONDRIAL-DNA
    YEN, TC
    PANG, CY
    HSIEH, RH
    SU, CH
    KING, KL
    WEI, YH
    BIOCHEMISTRY INTERNATIONAL, 1992, 26 (03): : 457 - 468
  • [47] Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: Implications for genotoxic mechanisms in mammalian cells
    Partridge, Michael A.
    Huang, Sarah X. L.
    Hernandez-Rosa, Evelyn
    Davidson, Mercy M.
    Hei, Tom K.
    CANCER RESEARCH, 2007, 67 (11) : 5239 - 5247
  • [48] Age-dependent impairment of mitochondrial function in rat heart tissue - Effect of pharmacological agents
    Paradies, G
    Ruggiero, FM
    Petrosillo, G
    Quagliariello, E
    PHARMACOLOGICAL INTERVENTION IN AGING AND AGE-ASSOCIATED DISORDERS: PROCEEDINGS OF THE SIXTH CONGRESS OF THE INTERNATIONAL ASSOCIATION OF BIOMEDICAL GERONTOLOGY, 1996, 786 : 252 - 263
  • [49] Increase of mitochondrial mass and mitochondrial DNA content as a response to oxidative stress of human cells harboring mitochondrial DNA mutation
    Wei, YH
    Lee, CF
    Liu, CY
    Lee, HC
    Ma, YS
    Pang, CY
    MICRONUTRIENTS AND HEALTH: MOLECULAR BIOLOGICAL MECHANISMS, 2001, : 168 - 183
  • [50] Enhanced oxidative damage in human cells harboring A3243G mutation of mitochondrial DNA: implication of oxidative stress in the pathogenesis of mitochondrial diabetes
    Pang, CY
    Lee, HC
    Wei, YH
    DIABETES RESEARCH AND CLINICAL PRACTICE, 2001, 54 : S45 - S56