Cytochrome c Oxidase and the Regulation of Oxidative Phosphorylation

Abstract

Life of higher organisms is essentially dependent on the efficient synthesis of ATP by oxidative phosphorylation in mitochondria. An important and as yet unsolved question of energy metabolism is how are the variable rates of ATP synthesis at maximal work load during exercise or mental work and at rest or during sleep regulated. This article reviews our present knowledge on the structure of bacterial and eukaryotic cytochrome c oxidases and correlates it with recent results on the regulatory functions of nuclear-coded subunits of the eukaryotic enzyme, which are absent from the bacterial enzyme. A new molecular hypothesis on the physiological regulation of oxidative phosphorylation is proposed, assuming a hormonally controlled dynamic equilibrium in vivo between two states of energy metabolism, a relaxed state with low ROS (reactive oxygen species) formation, and an excited state with elevated formation of ROS, which are known to accelerate aging and to cause degenerative diseases and cancer. The hypothesis is based on the allosteric ATP inhibition of cytochrome c oxidase at high intramitochondrial ATP/ADP ratios ("second mechanism of respiratory control"), which is switched on by cAMP-dependent phosphorylation and switched off by calcium-induced dephosphorylation of the enzyme.

The Influence of Calcium on the Growth, Morphology and Gene Regulation in Gemmatimonas phototrophica

“…Much less is known about the specific role of calcium in prokaryotic cells. Calcium is required for the bacterial cytochrome c oxidase [ 33 , 34 , 35 ], which is in agreement with our finding that genes for this enzyme were up-regulated when more calcium was supplied. It is reported that calcium ions may play an essential role in chemotaxis, cell cycle, and competence by using calcium ions from an external source and calcium antagonists in prokaryotes [ 36 , 37 , 38 ].…”

The Influence of Calcium on the Growth, Morphology and Gene Regulation in Gemmatimonas phototrophica

“…Much less is known about the specific role of calcium in prokaryotic cells. Calcium is required for the bacterial cytochrome c oxidase [ 33 , 34 , 35 ], which is in agreement with our finding that genes for this enzyme were up-regulated when more calcium was supplied. It is reported that calcium ions may play an essential role in chemotaxis, cell cycle, and competence by using calcium ions from an external source and calcium antagonists in prokaryotes [ 36 , 37 , 38 ].…”

PACT establishes a posttranscriptional brake on mitochondrial biogenesis by promoting the maturation of miR-181c

“…Of note, our data indicates that PACT and miR-181c′s impact on OXPHOS activity is mostly through complex IV regulation. As complex IV is an exception for not producing ROS during reduction of oxygen ( 67 ) and its activity was significantly increased with PACT or miR-181c deletion, our data suggests that PACT exerts its effect on mitochondrial respiration and ROS production via impacting complex IV activity. Further investigation of the activity of all ETC complexes in the context of PACT and miR-181c is crucial to fully understand how this axis regulates mitochondrial functioning.…”

Therapeutic Potential of Photobiomodulation In Alzheimer’s Disease: A Systematic Review

“…The CCO has the function of reducing oxygen and water, facilitating electrons transference in the mitochondrial membrane, and promoting changes in molecular levels due to increased cellular metabolism. 43,44 In this sense, these data suggest that photobiomodulation may restore mitochondrial damage observed in AD by increasing CCO levels.…”

The Influence of Calcium on the Growth, Morphology and Gene Regulation in Gemmatimonas phototrophica

“…Much less is known about the specific role of calcium in prokaryotic cells. Calcium is required for the bacterial cytochrome c oxidase [ 33 , 34 , 35 ], which is in agreement with our finding that genes for this enzyme were up-regulated when more calcium was supplied. It is reported that calcium ions may play an essential role in chemotaxis, cell cycle, and competence by using calcium ions from an external source and calcium antagonists in prokaryotes [ 36 , 37 , 38 ].…”

PACT establishes a posttranscriptional brake on mitochondrial biogenesis by promoting the maturation of miR-181c

“…Of note, our data indicates that PACT and miR-181c′s impact on OXPHOS activity is mostly through complex IV regulation. As complex IV is an exception for not producing ROS during reduction of oxygen ( 67 ) and its activity was significantly increased with PACT or miR-181c deletion, our data suggests that PACT exerts its effect on mitochondrial respiration and ROS production via impacting complex IV activity. Further investigation of the activity of all ETC complexes in the context of PACT and miR-181c is crucial to fully understand how this axis regulates mitochondrial functioning.…”

Therapeutic Potential of Photobiomodulation In Alzheimer’s Disease: A Systematic Review

“…The CCO has the function of reducing oxygen and water, facilitating electrons transference in the mitochondrial membrane, and promoting changes in molecular levels due to increased cellular metabolism. 43,44 In this sense, these data suggest that photobiomodulation may restore mitochondrial damage observed in AD by increasing CCO levels.…”

The Influence of Calcium on the Growth, Morphology and Gene Regulation in Gemmatimonas phototrophica

“…Much less is known about the specific role of calcium in prokaryotic cells. Calcium is required for the bacterial cytochrome c oxidase [ 33 , 34 , 35 ], which is in agreement with our finding that genes for this enzyme were up-regulated when more calcium was supplied. It is reported that calcium ions may play an essential role in chemotaxis, cell cycle, and competence by using calcium ions from an external source and calcium antagonists in prokaryotes [ 36 , 37 , 38 ].…”

PACT establishes a posttranscriptional brake on mitochondrial biogenesis by promoting the maturation of miR-181c

“…Of note, our data indicates that PACT and miR-181c′s impact on OXPHOS activity is mostly through complex IV regulation. As complex IV is an exception for not producing ROS during reduction of oxygen ( 67 ) and its activity was significantly increased with PACT or miR-181c deletion, our data suggests that PACT exerts its effect on mitochondrial respiration and ROS production via impacting complex IV activity. Further investigation of the activity of all ETC complexes in the context of PACT and miR-181c is crucial to fully understand how this axis regulates mitochondrial functioning.…”

Therapeutic Potential of Photobiomodulation In Alzheimer’s Disease: A Systematic Review

“…The CCO has the function of reducing oxygen and water, facilitating electrons transference in the mitochondrial membrane, and promoting changes in molecular levels due to increased cellular metabolism. 43,44 In this sense, these data suggest that photobiomodulation may restore mitochondrial damage observed in AD by increasing CCO levels.…”