Melatonin and mitochondrial function

被引:290
作者
Leon, J
Acuña-Castroviejo, D
Sainz, RM
Mayo, JC
Tan, DX
Reiter, RJ
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Cell & Struct Biol, San Antonio, TX 78229 USA
[2] Univ Granada, Dept Fisiol, Fac Med, Inst Biotecnol, Granada, Spain
关键词
melatonin; mitochondria; reactive oxygen species; reactive nitrogen species; Parkinson's disease; Alzheimer's disease; aging; sepsis; ischemia-reperfusion;
D O I
10.1016/j.lfs.2004.03.003
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Melatonin is a natural occurring compound with well-known antioxidant properties. In the last decade a new effect of melatonin on mitochondrial homeostasis has been discovered and, although the exact molecular mechanism for this effect remains unknown, it may explain, at least in part, the protective properties found for the indoleamine in degenerative conditions such as aging as well as Parkinson's disease, Alzheimer's disease, epilepsy, sepsis and other injuries such as ischemia-reperfusion. A common feature in these diseases is the existence of mitochondrial damage due to oxidative stress, which may lead to a decrease in the activities of mitochondrial complexes and ATP production, and, as a consequence, a further increase in free radical generation. A vicious cycle thus results under these conditions of oxidative stress with the final consequence being cell death by necrosis or apoptosis. Melatonin is able of directly scavenging a variety of toxic oxygen and nitrogen-based reactants, stimulates antioxidative enzymes, increases the efficiency of the electron transport chain thereby limiting electron leakage and free radical generation, and promotes ATP synthesis. Via these actions, melatonin preserves the integrity of the mitochondria and helps to maintain cell functions and survival. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:765 / 790
页数:26
相关论文
共 217 条
[51]  
Fosslien E, 2001, ANN CLIN LAB SCI, V31, P25
[52]   SUPEROXIDE RADICAL AND SUPEROXIDE DISMUTASES [J].
FRIDOVICH, I .
ANNUAL REVIEW OF BIOCHEMISTRY, 1995, 64 :97-112
[53]   Role of pinoline and melatonin in stabilizing hepatic microsomal membranes against oxidative stress [J].
García, JJ ;
Reiter, RJ ;
Pié, J ;
Ortiz, GG ;
Cabrera, J ;
Sáinz, RM ;
Acuña-Castroviejo, D .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1999, 31 (06) :609-616
[54]   Melatonin preserves arachidonic and docosapentaenoic acids during ascorbate-Fe2+ peroxidation of rat testis microsomes and mitochondria [J].
Gavazza, M ;
Catalá, A .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2003, 35 (03) :359-366
[55]   The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2 [J].
Genova, ML ;
Ventura, B ;
Giuliano, G ;
Bovina, C ;
Formiggini, G ;
Castelli, GP ;
Lenaz, G .
FEBS LETTERS, 2001, 505 (03) :364-368
[56]   Mitochondrial production of oxygen radical species and the role of coenzyme Q as an antioxidant [J].
Genova, MW ;
Pich, MM ;
Biondi, A ;
Bernacchia, A ;
Falasca, A ;
Bovina, C ;
Formiggini, G ;
Castelli, GP ;
Lenaz, G .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2003, 228 (05) :506-513
[57]   Mitochondrial nitric-oxide synthase stimulation causes cytochrome c release from isolated mitochondria -: Evidence for intramitochondrial peroxynitrite formation [J].
Ghafourifar, P ;
Schenk, U ;
Klein, SD ;
Richter, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (44) :31185-31188
[58]   Nitric oxide synthase activity in mitochondria [J].
Ghafourifar, P ;
Richter, C .
FEBS LETTERS, 1997, 418 (03) :291-296
[59]   Characterization and function of mitochondrial nitricoxide synthase [J].
Giulivi, C .
FREE RADICAL BIOLOGY AND MEDICINE, 2003, 34 (04) :397-408
[60]   Functional implications of nitric oxide produced by mitochondria in mitochondrial metabolism [J].
Giulivi, C .
BIOCHEMICAL JOURNAL, 1998, 332 :673-679