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, 748, 1-11

Introduction to Mitochondrial Oxidative Phosphorylation

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Introduction to Mitochondrial Oxidative Phosphorylation

Bernhard Kadenbach. Adv Exp Med Biol.

Abstract

The basic mechanism of ATP synthesis in the mitochondria by oxidative phosphorylation (OxPhos) was revealed in the second half of the twentieth century. The OxPhos complexes I-V have been analyzed concerning their subunit composition, genes, and X-ray structures. This book presents new developments regarding the morphology, biogenesis, gene evolution, heat, and reactive oxygen species (ROS) generation in mitochondria, as well as the structure and supercomplex formation of OxPhos complexes. In addition, multiple mitochondrial diseases based on mutations of nuclear-encoded genes have been identified. Little is known, however, of the regulation of OxPhos according to the variable cellular demands of ATP. In particular, the functions of the supernumerary (nuclear-encoded) subunits of mitochondrial OxPhos complexes, which are mostly absent in bacteria, remain largely unknown, although the corresponding and conserved core subunits exhibit the same catalytic activity. Identification of regulatory pathways modulating OxPhos activity, by subunit isoform expression, by allosteric interaction with ATP/ADP, by reversible phosphorylation of protein subunits, or by supercomplex formation, will help to understand the role of mitochondria in the many degenerative diseases, mostly based on ROS formation in mitochondria and/or insufficient energy production.

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