Cytochrome c Oxidase at Full Thrust: Regulation and Biological Consequences to Flying Insects
Open Access
- 22 February 2021
- Vol. 10 (2), 470
- https://doi.org/10.3390/cells10020470
Abstract
Flight dispersal represents a key aspect of the evolutionary and ecological success of insects, allowing escape from predators, mating, and colonization of new niches. The huge energy demand posed by flight activity is essentially met by oxidative phosphorylation (OXPHOS) in flight muscle mitochondria. In insects, mitochondrial ATP supply and oxidant production are regulated by several factors, including the energy demand exerted by changes in adenylate balance. Indeed, adenylate directly regulates OXPHOS by targeting both chemiosmotic ATP production and the activities of specific mitochondrial enzymes. In several organisms, cytochrome c oxidase (COX) is regulated at transcriptional, post-translational, and allosteric levels, impacting mitochondrial energy metabolism, and redox balance. This review will present the concepts on how COX function contributes to flying insect biology, focusing on the existing examples in the literature where its structure and activity are regulated not only by physiological and environmental factors but also how changes in its activity impacts insect biology. We also performed in silico sequence analyses and determined the structure models of three COX subunits (IV, VIa, and VIc) from different insect species to compare with mammalian orthologs. We observed that the sequences and structure models of COXIV, COXVIa, and COXVIc were quite similar to their mammalian counterparts. Remarkably, specific substitutions to phosphomimetic amino acids at critical phosphorylation sites emerge as hallmarks on insect COX sequences, suggesting a new regulatory mechanism of COX activity. Therefore, by providing a physiological and bioenergetic framework of COX regulation in such metabolically extreme models, we hope to expand the knowledge of this critical enzyme complex and the potential consequences for insect dispersal.Funding Information
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (001)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (404153/2016-0, 483334/2013-8, 402409/2012-4, 314717/2020-0, 303044/2017-9)
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (E-26/102.333/2013, E-26/203.043/2016, E-26/111.169/2011, E-44/208702/2014)
This publication has 182 references indexed in Scilit:
- Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissuesNature Communications, 2012
- Protein Phosphorylation and Prevention of Cytochrome Oxidase Inhibition by ATP: Coupled Mechanisms of Energy Metabolism RegulationCell Metabolism, 2011
- Cytochrome c oxidase loses catalytic activity and structural integrity during the aging process in Drosophila melanogasterBiochemical and Biophysical Research Communications, 2010
- Cyclic AMP Produced inside Mitochondria Regulates Oxidative PhosphorylationCell Metabolism, 2009
- Age-related decrease in expression of mitochondrial DNA encoded subunits of cytochrome c oxidase in Drosophila melanogasterMechanisms of Ageing and Development, 2008
- A Conserved Steroid Binding Site in Cytochrome c OxidaseBiochemistry, 2008
- The nature of flightEMBO Reports, 2007
- Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusionFEBS Letters, 2007
- Flux control and excess capacity in the enzymes of glycolysis and their relationship to flight metabolism inDrosophila melanogasterProceedings of the National Academy of Sciences of the United States of America, 2006
- Cytochrome c oxidase subunit IV is essential for assembly and respiratory function of the enzyme complexJournal of Bioenergetics and Biomembranes, 2006