The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure

• Published in: Cell metabolism Vol. 33; no. 3; pp. 629 - 648.e10
• Main Authors: Cluntun, Ahmad A., Badolia, Rachit, Lettlova, Sandra, Parnell, K. Mark, Shankar, Thirupura S., Diakos, Nikolaos A., Olson, Kristofor A., Taleb, Iosif, Tatum, Sean M., Berg, Jordan A., Cunningham, Corey N., Van Ry, Tyler, Bott, Alex J., Krokidi, Aspasia Thodou, Fogarty, Sarah, Skedros, Sophia, Swiatek, Wojciech I., Yu, Xuejing, Luo, Bai, Merx, Shannon, Navankasattusas, Sutip, Cox, James E., Ducker, Gregory S., Holland, William L., McKellar, Stephen H., Rutter, Jared, Drakos, Stavros G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.03.2021
• Subjects: Animals; Anion Transport Proteins - antagonists & inhibitors; Anion Transport Proteins - genetics; Anion Transport Proteins - metabolism; cardiac metabolism; Cardiomegaly - chemically induced; Cardiomegaly - complications; Cardiomegaly - pathology; heart failure; Heart Failure - etiology; Heart Failure - pathology; Heart-Assist Devices; Humans; hypertrophy; lactate; Lactic Acid - metabolism; LVAD; MCT4; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Mice, Knockout; mitochondria; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins - antagonists & inhibitors; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Membrane Transport Proteins - metabolism; Monocarboxylic Acid Transporters - antagonists & inhibitors; Monocarboxylic Acid Transporters - genetics; Monocarboxylic Acid Transporters - metabolism; MPC; Muscle Proteins - antagonists & inhibitors; Muscle Proteins - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; pyruvate; Pyruvic Acid - metabolism; Reactive Oxygen Species - metabolism; RNA Interference; RNA, Small Interfering - metabolism; VB124; Ventricular Function, Left - physiology; heart failure; MPC; MCT4; hypertrophy; cardiac metabolism; mitochondria; lactate; pyruvate; VB124; LVAD

The metabolic rewiring of cardiomyocytes is a widely accepted hallmark of heart failure (HF). These metabolic changes include a decrease in mitochondrial pyruvate oxidation and an increased export of lactate. We identify the mitochondrial pyruvate carrier (MPC) and the cellular lactate exporter mono...