Protein Kinase A Governs Oxidative Phosphorylation Kinetics and Oxidant Emitting Potential at Complex I

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Daniel S.,Reese,Lauren R.,Ryan,Terence E.,Torres,Maria J. Lark (Creator)
East Carolina University (ECU )
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Abstract: he mitochondrial electron transport system (ETS) is responsible for setting andmaintaining both the energy and redox charges throughout the cell. Reversiblephosphorylation of mitochondrial proteins, particularly via the soluble adenylyl cyclase(sAC)/cyclic AMP (cAMP)/Protein kinase A (PKA) axis, has recently been revealed asa potential mechanism regulating the ETS. However, the governance of cAMP/PKAsignaling and its implications on ETS function are incompletely understood. In contrastto prior reports using exogenous bicarbonate, we provide evidence that endogenousCO2 produced by increased tricarboxylic acid (TCA) cycle flux is insufficient to increasemitochondrial cAMP levels, and that exogenous addition of membrane permeant8Br-cAMP does not enhance mitochondrial respiratory capacity. We also reportimportant non-specific effects of commonly used inhibitors of sAC which preclude theiruse in studies of mitochondrial function. In isolated liver mitochondria, inhibition of PKAreduced complex I-, but not complex II-supported respiratory capacity. In permeabilizedmyofibers, inhibition of PKA lowered both the Km and Vmax for complex I-supportedrespiration as well as succinate-supported H2O2 emitting potential. In summary, thedata provided here improve our understanding of how mitochondrial cAMP productionis regulated, illustrate a need for better tools to examine the impact of sAC activityon mitochondrial biology, and suggest that cAMP/PKA signaling contributes to thegovernance of electron flow through complex I of the ETS.

Additional Information

Language: English
Date: 2015
mitochondria, adenylyl cyclase, cAMP, protein kinase A, complex I, respiration, skeletal muscle, liver

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