Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38769288.
- Also identified by DOI 10.1038/s41467-024-48474-z and PMC identifier 11106256.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Elevated intracellular sodium Na<sub>i</sub> adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Na<sub>i</sub> decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH<sub>2</sub>, which are all reversed on lowering Na<sub>i</sub> to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Na<sub>i</sub> elevation. Elevated Na<sub>i</sub> plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.
Medical subject headings
- Mitochondria, Heart
- Sodium