New extension of the Mitchell Theory for oxidative phosphorylation in mitochondria of living organisms

被引:92
作者
Kadenbach, Bernhard [1 ]
Ramzan, Rabia [1 ]
Wen, Li [2 ]
Vogt, Sebastian [2 ]
机构
[1] Univ Marburg, Fachbereich Chem, Cardiovasc Lab, D-35032 Marburg, Germany
[2] Univ Marburg, Biomed Res Ctr, Cardiovasc Lab, D-35032 Marburg, Germany
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2010年 / 1800卷 / 03期
关键词
Mitochondrial membrane potential; Hyperpolarization; Mitchell Theory; Cytochrome c oxidase; Degenerative disease; Oxidative stress; Protein phosphorylation; CYTOCHROME-C-OXIDASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; BOVINE HEART-MITOCHONDRIA; IN-VIVO CONTROL; REACTIVE OXYGEN; PROTEIN-KINASE; SUBUNIT-IV; COMPLEX-I; RESPIRATORY-CHAIN; HUMAN-DISEASE;
D O I
10.1016/j.bbagen.2009.04.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Mitchell Theory implies the proton motive force Delta p across the inner mitochondrial membrane as the energy-rich intermediate of oxidative phosphorylation. Delta p is composed mainly of an electrical (Delta Psi(m)) and a chemical part (Delta pH) and generated by the respiratory chain complexes I, III and IV. It is consumed mostly by the ATP synthase (complex V) to produce ATP. The free energy of electron transport within the proton pumps is sufficient to generate Delta p of about 240 mV. The proton permeability of biological membranes, however, increases exponentially above 130 mV leading to a waste of energy at high values (Delta Psi(m) >140 mV). In addition, at Delta Psi(m) > 140 mV, the production of the superoxide radical anion O(2)(-) at complexes I, II and III increases exponentially with increasing Delta Psi(m). O(2)(-). and its neutral product H(2)O(2) (=ROS, reactive oxygen species) induce oxidative stress which participates in aging and in the generation of degenerative diseases. Here we describe a new mechanism which acts independently of the Mitchell Theory and keeps Delta Psi(m) at low values through feedback inhibition of complex IV (cytochrome c oxidase) at high ATP/ADP ratios, thus preventing the formation of ROS and maintaining high efficiency of oxidative phosphorylation. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:205 / 212
页数:8
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