Details

Autor(en) / Beteiligte

• Dambrova, Maija
• Zuurbier, Coert J.
• Borutaite, Vilmante
• Liepinsh, Edgars
• Makrecka-Kuka, Marina

Titel

Energy substrate metabolism and mitochondrial oxidative stress in cardiac ischemia/reperfusion injury

Ist Teil von

• Free radical biology & medicine, 2021-03, Vol.165, p.24-37

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The heart is the most metabolically flexible organ with respect to the use of substrates available in different states of energy metabolism. Cardiac mitochondria sense substrate availability and ensure the efficiency of oxidative phosphorylation and heart function. Mitochondria also play a critical role in cardiac ischemia/reperfusion injury, during which they are directly involved in ROS-producing pathophysiological mechanisms. This review explores the mechanisms of ROS production within the energy metabolism pathways and focuses on the impact of different substrates. We describe the main metabolites accumulating during ischemia in the glucose, fatty acid, and Krebs cycle pathways. Hyperglycemia, often present in the acute stress condition of ischemia/reperfusion, increases cytosolic ROS concentrations through the activation of NADPH oxidase 2 and increases mitochondrial ROS through the metabolic overloading and decreased binding of hexokinase II to mitochondria. Fatty acid-linked ROS production is related to the increased fatty acid flux and corresponding accumulation of long-chain acylcarnitines. Succinate that accumulates during anoxia/ischemia is suggested to be the main source of ROS, and the role of itaconate as an inhibitor of succinate dehydrogenase is emerging. We discuss the strategies to modulate and counteract the accumulation of substrates that yield ROS and the therapeutic implications of this concept. Changes in cardiac content of metabolic intermediates during ischemia. [Display omitted] •Energy metabolites accumulate during I/R and drive ROS formation in the heart.•High glucose produces ROS through NOX2, increased ψm and decreased mitoHKII.•Fatty acid-linked ROS production is related to accumulation of long-chain acylcarnitines.•Inhibiting SDH might prevent succinate-driven ROS formation during the perfusion.•Therapies that target metabolite accumulation protect the heart from I/R injury.