ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
A mitochondrial CO2-adenylyl cyclase-cAMP signalosome controls yeast normoxic cytochrome c oxidase activity.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Profiling of Yeast Saccharomyces cerevisiae Mitochondrial AMPylome Reveals a Regulation of OXPHOS Coupling through ATP Synthase Subunit Delta.Journal of proteome research · 2026Article
- The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation.Biophysical reviews · 2025Review
- Advances inJournal of fungi (Basel, Switzerland) · 2023Review
- Comprehensive Interactome Analysis for the Sole Adenylyl Cyclase Cyr1 of Candida albicans.Microbiology spectrum · 2022Article
- Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential.Frontiers in physiology · 2022Article
- Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology.Life (Basel, Switzerland) · 2021Review
- CytochromeCells · 2021Review
- Regulation of Mitochondrial Homeostasis by sAC-Derived cAMP Pool: Basic and Translational Aspects.Cells · 2021Review
- Mitochondrial respiratory chain composition and organization in response to changing oxygen levels.Journal of life sciences (Westlake Village, Calif.) · 2020Article
- The molecular biology of fruity and floral aromas in beer and other alcoholic beverages.FEMS microbiology reviews · 2019Review
- Multiple-Omics Techniques Reveal the Role of Glycerophospholipid Metabolic Pathway in the Response ofFrontiers in microbiology · 2019Article
- Structure of yeast cytochrome c oxidase in a supercomplex with cytochrome bcNature structural & molecular biology · 2019Article
- 17β-Estradiol reduces mitochondrial cAMP content and cytochrome oxidase activity in a phosphodiesterase 2-dependent manner.British journal of pharmacology · 2018Article
- Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments.Journal of cardiovascular development and disease · 2018Review
- Distinct intracellular sAC-cAMP domains regulate ER CaJournal of cell science · 2017Article
- Mitochondrial cAMP signaling.Cellular and molecular life sciences : CMLS · 2016Review
- Soluble adenylyl cyclase is essential for proper lysosomal acidification.The Journal of general physiology · 2016Article
- Article
- Revisiting Kadenbach: Electron flux rate through cytochrome c-oxidase determines the ATP-inhibitory effect and subsequent production of ROS.BioEssays : news and reviews in molecular, cellular and developmental biology · 2016Review
- Molecular Mechanisms and Therapeutic Effects of (-)-Epicatechin and Other Polyphenols in Cancer, Inflammation, Diabetes, and Neurodegeneration.Oxidative medicine and cellular longevity · 2015Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Mitochondria, the major source of cellular energy in the form of ATP, respond to changes in substrate availability and bioenergetic demands by employing rapid, short-term, metabolic adaptation mechanisms, such as phosphorylation-dependent protein regulation. In mammalian cells, an intramitochondrial CO2-adenylyl cyclase (AC)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway regulates aerobic energy production. One target of this pathway involves phosphorylation of cytochrome c oxidase (COX) subunit 4-isoform 1 (COX4i1), which modulates COX allosteric regulation by ATP. However, the role of the CO2-sAC-cAMP-PKA signalosome in regulating COX activity and mitochondrial metabolism and its evolutionary conservation remain to be fully established. We show that in Saccharomyces cerevisiae, normoxic COX activity measured in the presence of ATP is 55% lower than in the presence of ADP. Moreover, the adenylyl cyclase Cyr1 activity is present in mitochondria, and it contributes to the ATP-mediated regulation of COX through the normoxic subunit Cox5a, homologue of human COX4i1, in a bicarbonate-sensitive manner. Furthermore, we have identified 2 phosphorylation targets in Cox5a (T65 and S43) that modulate its allosteric regulation by ATP. These residues are not conserved in the Cox5b-containing hypoxic enzyme, which is not regulated by ATP. We conclude that across evolution, a CO2-sAC-cAMP-PKA axis regulates normoxic COX activity.
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