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Cell Biological Consequences of OXPHOS Disorders

  • Chapter
Oxidative Phosphorylation in Health and Disease

Part of the book series: Medical Intelligence Unit ((MIUN))

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Abstract

During the past century mitochondria have been recognized to play a central role in many cellular functions. Apart from producing cellular energy in the form of ATP (adenosine 5′-triphosphate) this organelle harbors essential parts of the urea cycle and is crucial for the breakdown of fatty acids, heat generation and the biosynthesis of heme, pyrimidines, amino acids, phospholipids and nucleotides. In addition to these ‘classical’ functions, mitochondria are also key players in cellular signaling through their involvement in apoptosis, generation of reactive nitrogen- and oxygen species (ROS/RNS), transduction of electrical signals and calcium homeostasis. This chapter summarizes current insights concerning the consequences of oxidative phosphorylation (OXPHOS) dysfunction at the cellular level. We will start with illustrating how mitochondrial and cellular metabolism is intertwined during ATP generation, calcium transport and ROS production. Moreover, the relation between mitochondrial morphology and function will be addressed. Next, we will summarize how OXPHOS deficiency and cellular functioning have been analyzed using pharmacological model systems and patient-derived cell lines. Also results of mathematical modeling, applied to integrate and understand the complex experimental data, will be treated. Finally, we will discuss possible adaptive mechanisms that counterbalance OXPHOS deficiency in the living cell.

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Authors and Affiliations

  1. Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, University Medical Center, Nijmegen, The Netherlands

    Werner J. H. Koopman & Peter H. G. M. Willems

  2. Department of Biochemistry, Nijmegen Center for Molecular Life Sciences and Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center, Nijmegen, The Netherlands

    Henk-Jan Visch & Sjoerd Verkaart

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Koopman, W.J.H., Visch, HJ., Verkaart, S., Willems, P.H.G.M. (2004). Cell Biological Consequences of OXPHOS Disorders. In: Oxidative Phosphorylation in Health and Disease. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-26992-4_8

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