Interaction of mtROS-Immune-Inflammatory Vicious Cycle Activation in Sepsis-Induced Cardiomyopathy

Mitochondrial reactive oxygen species (mtROS) serve as a central mediator in the pathogenesis of mitochondrial energy metabolism disorders and play a pivotal role in sepsis-induced cardiomyopathy (SICM). The production and regulation of mtROS involve multiple molecular mechanisms, including VDAC1-mediated mitochondrial impairment and the STK3/KEAP1/Nrf2 signalling pathway. Once generated, mtROS contribute to cellular damage through dual effects on the nitric oxide-lipid metabolic axis and complex interactions with ferroptosis. The pathological impact of mtROS is further amplified by mitochondria-endoplasmic reticulum interactions involving the DUSP1/PHB2 pathway. Critically, mtROS drive immune-related organ damage in sepsis by modulating the immune microenvironment, characterised by dynamic changes in cytokine storms, local cardiac immune cell infiltration, and aberrant activation of inflammatory signalling pathways. The SIRT3-SOD2 axis plays a key regulatory role in this process, as cardiac-specific overexpression of SOD2 improves heart function by controlling mtROS levels. Together, this review interconnected mechanisms establish mtROS as a central hub linking mitochondrial dysfunction, immune dysregulation, and myocardial injury in SICM, suggesting that targeting mtROS and its regulatory pathways represents a promising therapeutic strategy.