Mitochondrial energetics and calcium coupling in the heart. (10th March 2017)

• Record Type: Journal Article
• Authors: Kohlhaas, Michael; Nickel, Alexander G.; Maack, Christoph
• Is Part Of: Journal of physiology. Volume 595:Number 12(2017)
• Page Start: 3753
• Page End: 3763
• Publication Date: 2017-03-10
• Subjects: calcium mitochondria -- heart failure -- mitochondria -- reactive oxygen species -- redox; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP273609
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Mitochondrial redox balance is under the control of Ca 2+ and ADP in the normal heart and heart failure. Under physiological conditions, parallel activation of energy consumption (via force transduction) and energy regeneration (via Krebs cycle stimulation) by Ca 2+ balances the redox states of NADH/NAD + and NADPH/NADP +, maintaining reducing equivalents for ATP production and the antioxidative capacity. In heart failure, a mismatch of workload and mitochondrial Ca 2+ uptake induces a redox mismatch that results in oxidation of pyridine nucleotides and that accounts for energy deprivation and oxidative stress. Drugs directed against this mismatch and oxidative stress are indicated in pale brown (CGP‐37157, an inhibitor of the mitochondrial Na + /Ca 2+ exchanger; SS‐31, a tetrapeptide binding to cardiolipin; MitoQ, an antioxidant accumulating in mitochondria). ATP, adenosine triphosphate; cyto, cytosolic; ETC, electron transport chain; mito, mitochondrial; ROS, reactive oxygen species; SR, sarcoplasmic reticulum. Abstract: Contraction and relaxation of the heart consume large amounts of energy that need to be replenished by oxidative phosphorylation in mitochondria, and matching energy supply to demand involves the complimentary control of respiration through ADP and Ca 2+ . In heart failure, an imbalance between ADP and Ca 2+ leads to oxidation of mitochondrial pyridine nucleotides, where NADH oxidation may limit ATP production and contractile function, while NADPH oxidation can induce oxidative stress with consecutive maladaptive remodelling. Understanding the complex mechanisms that disturb this finely tuned equilibrium may aid the development of drugs that could ameliorate the progression of heart failure beyond the classical neuroendocrine inhibition.