The potential mechanism of mitochondrial dysfunction in septic cardiomyopathy

Abstract

Septic cardiomyopathy is one of the most serious complications of sepsis or septic shock. Basic and clinical research has studied the mechanism of cardiac dysfunction for more than five decades. It has become clear that myocardial depression is not related to hypoperfusion. As the heart is highly dependent on abundant adenosine triphosphate (ATP) levels to maintain its contraction and diastolic function, impaired mitochondrial function is lethally detrimental to the heart. Research has shown that mitochondria play an important role in organ damage during sepsis. The mitochondria-related mechanisms in septic cardiomyopathy have been discussed in terms of restoring mitochondrial function. Mitochondrial uncoupling proteins located in the mitochondrial inner membrane can promote proton leakage across the mitochondrial inner membrane. Recent studies have demonstrated that proton leakage is the essential regulator of mitochondrial membrane potential and the generation of reactive oxygen species (ROS) and ATP. Other mechanisms involved in septic cardiomyopathy include mitochondrial ROS production and oxidative stress, mitochondria Ca2+ handling, mitochondrial DNA in sepsis, mitochondrial fission and fusion, mitochondrial biogenesis, mitochondrial gene regulation and mitochondria autophagy. This review will provide an overview of recent insights into the factors contributing to septic cardiomyopathy.

Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications

“…Mitochondria seem to play an important role in organ damage during sepsis. 69 Myocardial injury during sepsis leading to LV dysfunction portends a poor prognosis. It has been suggested that the pathophysiology of sepsisinduced cardiac dysfunction may relate to increased oxidative stress, active inflammation, impaired β-adrenergic signaling, enhanced apoptosis, suppression of metabolic pathways, and decreased ATP synthesis in the cardiomyocytes.…”

The Role of Autophagy in Sepsis: Protection and Injury to Organs

“…The autophagic receptor protein SQSTM1/p62 acts to recognize ubiquitinated mitochondrial proteins and link them, through binding to LC3 to autophagosome (Preau et al, 2016). Damaged mitochondria are isolated by autophagosomes and eventually degraded by fusion with lysosomes, promoting the recovery of septic organ function (Bartz et al, 2015; Pan et al, 2018). Another key transcription factor for mitochondrial quality control is nuclear factor erythroid 2-related factor 2 (Nrf2) (Stępkowski and Kruszewski, 2011).…”

“…Prompt removal of damaged mitochondria can prevent oxidative damage. Otherwise, oxidative damage may cause apoptosis, leading to worsening of myocardial damage in sepsis (Pan et al, 2018). Beclin-1 promotes mitochondrial biogenesis via PINK1/Parkin as well as AMPK/ULK1, and also selectively facilitates PINK1-Parkin mitophagy for the clearance of damaged mitochondria.…”

Quantitative proteomic analysis of mitochondrial proteins differentially expressed between small cell lung cancer cells and normal human bronchial epithelial cells

“…Mitochondria are ubiquitous cellular organelles that are responsible for energy metabolism in eukaryotic cells and have been associated with various conditions, including Alzheimer's disease, Parkinson's disease, diabetes mellitus, various cardiovascular diseases, and lung cancer . Mitochondrial DNA mutations and associated disorders are also related to tumor development, growth, angiogenesis, and metastasis .…”