Preventing mitochondrial reverse electron transport as a strategy for cardioprotection

Abstract

In the context of myocardial infarction, the burst of superoxide generated by reverse electron transport (RET) at complex I in mitochondria is a crucial trigger for damage during ischaemia/reperfusion (I/R) injury. Here we outline the necessary conditions for superoxide production by RET at complex I and how it can occur during reperfusion. In addition, we explore various pathways that are implicated in generating the conditions for RET to occur and suggest potential therapeutic strategies to target RET, aiming to achieve cardioprotection.

Mitochondrial calcium in cardiac ischemia/reperfusion injury and cardioprotection

“…The burst of mitochondrial superoxide occurring at the onset of reperfusion was initially considered a non-specific consequence of the restored availability of O 2 , but there is now robust evidence indicating that reverse electron transport (RET) at complex I of the respiratory chain is the primary source of superoxide during reperfusion [25]. The mechanistic underpinnings of this process and its role in I/R injury are discussed in detail in another review of this series [120]. Here, we outline the concept of redox-optimized ROS balance, a unifying framework that explains how the overflow of ROS is determined by the redox environment of the cell [5] and ROS-induced ROS release, a self-amplifying process that can exacerbate cardiac myocyte loss and induce arrhythmias during I/R injury [143].…”

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

“…Therefore, a more promising approach is to target succinate metabolism [ 374 ]. By inhibiting SDH, this can prevent succinate accumulation during ischemia or its oxidation during reperfusion.…”

Mitochondrial Kinase Signaling for Cardioprotection

“…The functional parameters affected by cardioprotective maneuvers include the preservation of respiration and ATP production, the reduction in reactive oxygen species (ROS) release at the onset of reperfusion, the inhibition of mitochondrial permeability transition pore (MPTP) opening at the beginning of reperfusion, the preservation of mitochondrial morphology, and the activation of mitophagy. For details on mitochondrial function in I/R injury, the reader is referred to recent articles [15][16][17][18][19][20]. Taken together, the cardioprotective maneuvers of IPC, RIC, or IPostC target the mitochondria and alter the function of the organelles.…”