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Introduction

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High-Yield Terms

  • Mitochondrial DNA (mtDNA): the circular genome found within mitochondria, encompasses genes involved in respiratory functions of this organelle

  • Electrochemical half-cell: consists of an electrode and an electrolyte, 2 half-cells compose an electrochemical cell that is capable of deriving energy from chemical reactions

  • Ubiquinone (CoQ): a mobile component of the electron transport chain that can undergo either 1- or 2-electron reactions, transfers electrons from complexes I and II to complex III

  • Chemiosmotic potential: more correctly referred to as proton motive force (PMF), refers to the electrochemical gradient formed across the inner mitochondrial membrane due to the transport of protons, H+, whose energy is used to drive ATP synthesis

  • Reactive oxygen species: any of a group of chemically reactive molecules containing oxygen, such as hydrogen peroxide and superoxide anion

  • Encephalomyopathy: a disorder most often resulting from a defect in mitochondrial function affecting both skeletal muscle and central nervous system function

  • Adaptive thermogenesis: the regulated production of heat in response to environmental changes in temperature and diet; for example, shivering in humans is adaptive thermogenesis

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Mitochondria

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Oxidative phosphorylation is a critical energy (ATP)–generating metabolic pathway that occurs within the mitochondria. Mitochondria evolved from a symbiotic relationship between aerobic bacteria and primordial eukaryotic cells. Mitochondria contain a 16-kb circular genome (mtDNA) that contains 37 genes critical for the processes oxidative phosphorylation. However, the mtDNA does not encode all of the proteins in the mitochondria. Over 900 mitochondrial proteins are actually encoded by the nuclear genome. Thirteen of the mtDNA genes encode protein subunits of respiratory complexes I, III, IV, and V. Only complex II is solely composed of proteins encoded by nuclear genes. The mtDNA genome also encodes 22 mitochondrial tRNAs and 2 rRNAs that are essential for translation of mtDNA transcripts.

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Mammalian cells can have hundreds to thousands of mitochondria, and each mitochondrion contains several mtDNA genomes. This phenomenon is referred to as heteroplasmy. Also, any given mitochondrion is not a discrete, autonomous organelle because it has the capacity to fuse with a neighboring mitochondrion in the near future. Therefore, the entire mitochondrial population within any given cell is in constant flux. The concept of heteroplasmy is significant in the context of inherited disorders in mitochondrial biogenesis (discussed below). It is why the spectrum of symptoms with these types of diseases can be quite broad. In addition, because of the stochastic nature of mitochondrial inheritance during cell division, a daughter cell can occasionally inherit a population of mitochondria whose ratio of mutant to wild-type mtDNA differs significantly from that of the parental cell.

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Normal biogenesis of mitochondria is triggered in response to changes in the ATP:ADP ratio and to activation of 5′ adenosine monophosphate–activated protein kinase (AMPK) (Chapter 34) which in turn results in increased expression of peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor-1 (NRF1). PGC-1α is a master transcriptional coactivator of numerous ...

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