Septic Cardiomyopathy and Mitochondrial Quality Control.
TL;DR
Preserving the dynamic equilibrium of MQC is crucial for preventing or reversing SCM and may present novel molecular targets and therapeutic strategies.
Abstract
Septic cardiomyopathy (SCM) is a prevalent and serious cardiac complication arising from sepsis-induced multiple organ dysfunction syndrome (MODS). The pathogenesis of SCM is complex and primarily involves immune-inflammatory responses, oxidative stress, programmed cell death, and mitochondrial dysfunction. In recent years, mitochondrial quality control (MQC) has attracted growing interest as a central mechanism for maintaining cellular homeostasis and myocardial energy metabolism in SCM. This review systematically summarizes recent advances in four key MQC mechanisms involved in SCM: (1) phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy; (2) mitochondrial dynamics, including dynamin-related protein 1 (Drp1)/fission protein 1 (FIS1)-driven fission and optic atrophy protein 1 (OPA1)/mitofusin (MFN)-regulated fusion; (3) mitochondrial biogenesis under the regulatory control of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)/nuclear respiratory factor 1 (NRF1)/mitochondrial transcription factor A (TFAM) axis; and (4) the mitochondrial unfolded protein response (UPRmt), which maintains mitochondrial proteostasis through mediators such as C/EBP homologous protein (CHOP), YME1-like protease (YME1L), and Overlapping activity with m-AAA protease 1 (OMA1). These mechanisms have been shown to work synergistically to regulate mitochondrial clearance, renewal, and functional maintenance. Any imbalance among them can exacerbate myocardial injury. This review also emphasizes the redox crosstalk between oxidative stress and immune inflammation, with an emphasis on the pivotal contributions of NADPH oxidase 2 (NOX2), high mobility group box 1 (HMGB1), and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in vascular endothelial dysfunction and cardiac depression. In conclusion, preserving the dynamic equilibrium of MQC is crucial for preventing or reversing SCM and may present novel molecular targets and therapeutic strategies.