Cytochrome c oxidase — structure, function, and physiology of a redox-driven molecular machine

Richter, O.-M. H.; Ludwig, Bernd

doi:10.1007/s10254-003-0006-0

Cited by 167 publications

(112 citation statements)

References 182 publications

(200 reference statements)

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“…Indirect calorimetric data obtained with a regular diet suggest that MOR Ϫ/Ϫ mice rely more on the oxidation of fatty acids and less on glycolysis during periods when they are not actively eating. This metabolic trait might be related to a constitutive increase in liver COIV expression, a key mitochondrial enzyme involved in cellular respiration (31). This fuel preference may account, at least partially, for the decreased fat deposition seen with a high-fat diet (32).…”

Section: Discussionmentioning

confidence: 99%

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

et al. 2005

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Using pharmacological tools, a role for opioid receptors in the regulation of food intake has been documented. However, the involvement of specific receptor subtypes remains questionable, and little information is available regarding a role for opioid receptors in energy metabolism. Using adult male mice lacking the -opioid receptor (MOR) gene (MOR ؊/؊ ), we show that the MOR is not essential for the maintenance of normal levels of ad libitum food intake but does modulate the efficiency of energy storage during high-fat diets through the regulation of energy partitioning. When fed a regular diet, MOR ؊/؊ mice displayed only subtle alterations in energy homeostasis, suggesting a relative overuse of fat as a fuel source in the fed state. When fed a high-fat diet, MOR ؊/؊ mice were resistant to obesity and impaired glucose tolerance, despite having similar energy intake to wild-type mice. This resistance to obesity was associated with a strong induction of the expression of key mitochondrial enzymes involved in fatty acid oxidation within skeletal muscle. This metabolic role of the MOR, which is consistent with the properties of a "thrifty gene," suggests that the MOR pathway is a potential target for pharmacological intervention in the treatment of obesity associated with the intake of fatty diets. Diabetes 54: 3510 -3516, 2005 T he endogenous opioid system encompasses cloned receptor populations (, ␦, and ) and ligands (␤-endorphin, the enkephalins, and the dynorphins). Extensive work indicates that the opioid system plays a role in the regulation of appetite. Opioid receptors and peptides are expressed in sites of the central nervous system that play a role in regulating feeding behavior, and pharmacological experiments using opioid receptor ligands show that agonists promote eating and antagonists decrease food intake, at least in the short term (1-3). Numerous pharmacological studies indicate that opioids also play a role in modulating the rewarding effects of food (3-5). In contrast, little information suggests that opioids have a role in energy metabolism (6 -8).The need to establish the specific role of the opioid receptors in energy homeostasis has led to studies using putative specific opioid receptor ligands or, more recently, antisense probes directed against specific exons of opioid receptor genes (3,9). Pharmacological studies suggest that the and pathways are part of an interconnected brain network and participate in the orexigenic effect of several peptides that regulate food intake (10 -13). However, the interpretation of these data is complicated by our poor knowledge of the in vivo selectivity of ligand-receptor interactions that have been established in vitro (9,14).Recent studies conducted in mutant mice null for the opioid receptors have complemented pharmacological approaches and clarified the role of each receptor in nociception, anxiety, and drug abuse (14). To further define the role of the -opioid receptor (MOR) pathway in energy homeostasis, we characterized mice lacking the MOR gene ...

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Section: Discussionmentioning

confidence: 99%

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

et al. 2005

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“…It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to proton efflux into the inter-membrane space (Richter and Ludwig, 2003). The complex consists of 13 subunits encoded by 3 mitochondrial and 17 nuclear genes (www.mitop.de/).…”

Section: Discussionmentioning

confidence: 99%

Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart

Preston¹,

Oberlin²,

Holmuhamedov³

et al. 2008

Mechanisms of Ageing and Development

124

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Aging is associated with progressive decline in energetic reserves compromising cardiac performance and tolerance to injury. Although deviations in mitochondrial functions have been documented in senescent heart, the molecular bases for the decline in energy metabolism are only partially understood. Here, high-throughput transcription profiles of genes coding for mitochondrial proteins in ventricles from adult (6-months) and aged (24-months) rats were compared using microarrays. Out of 614 genes encoding for mitochondrial proteins, 94 were differentially expressed with 95% downregulated in the aged. The majority of changes affected genes coding for proteins involved in oxidative phosphorylation (39), substrate metabolism (14) and tricarboxylic acid cycle (6). Compared to adult, gene expression changes in aged hearts translated into a reduced mitochondrial functional capacity, with decreased NADH-dehydrogenase and F0F1-ATPase complex activities and capacity for oxygen-utilization and ATP synthesis. Expression of genes coding for transcription co-activator factors involved in the regulation of mitochondrial metabolism and biogenesis were downregulated in aged ventricles without reduction in mitochondrial density. Thus, aging induces a selective decline in activities of oxidative phosphorylation complexes I and V within a broader transcriptional downregulation of mitochondrial genes, providing a substrate for reduced energetic efficiency associated with senescence.

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“…Analysis of crystal structures of both oxidases showed that the core subunits I, II and III (SUI, SUII and SUIII) are structurally and functionally related [3][4][5]. SUI contains both the heme moieties (a and a 3 ) and a copper ion (Cu B ), while SUII contains the Cu A center, which houses two copper ions in a mixed valence state.…”

Section: Introductionmentioning

confidence: 99%

Deciphering protein–protein interactions during the biogenesis of cytochrome c oxidase from Paracoccus denitrificans

Gurumoorthy

Ludwig

2014

The FEBS Journal

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Biogenesis of the mitochondrial cytochrome c oxidase (COX) is a complex process due to its numerous subunits encoded by two genomes, as well as the localization of redox centers deep within the membrane. Here, we have assessed the biogenesis of the homologous aa 3 -type oxidase of the soil bacterium Paracoccus denitrificans. First, protein partners were analyzed using various membrane solubilization strategies to show interactions between COX and CtaG, a chaperone implicated in Cu B site metallation. Using an unbiased MS approach after immunological pull-down from untreated or cross-linked membranes, we then extend our view towards a hypothetical 'biogenesis complex' by identifying two further metal-inserting chaperones, Surf1c and Sco, together with enzymes catalyzing heme a synthesis. Our study also tentatively supports previous speculation regarding the existence of a predominantly co-translational mechanism for cofactor insertion during COX biogenesis.

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Cytochrome c oxidase — structure, function, and physiology of a redox-driven molecular machine

Cited by 167 publications

References 182 publications

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart

Deciphering protein–protein interactions during the biogenesis of cytochrome c oxidase from Paracoccus denitrificans

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