Sepsis, a life-threatening condition characterized by organ dysfunction resulting from severe infection, has gained considerable attention for the involvement of mitochondrial (mt) dysfunction in disrupting cellular energy metabolism and exacerbating inflammatory injury through the release of mt components. During sepsis, damage to the mt electron transport chain (ETC) in various organs impairs the mitochondria's ability to sustain ATP production and effectively use oxygen. This dysfunction also increases mt membrane permeability, releasing mt damage-associated molecular patterns (DAMPs), i.e., proteins, phospholipids, metabolites, nucleic acids (NA), and reactive oxygen species (ROS). These DAMPs synergize with pathogen-associated molecular patterns (PAMPs) to amplify systemic inflammation and organ injury. Despite advances in understanding mt-driven metabolic and immune dysregulation, translating these insights into effective therapeutic interventions remains challenging. This review explores the dual role of mitochondria in sepsis, functioning both as central regulators of cellular metabolism and as key modulators of inflammatory responses. It evaluates mt-targeted therapeutic strategies, including metabolic reprogramming, induction of mt biogenesis, antioxidant approaches, and stabilization of mt membranes. Integrating findings from both preclinical and clinical studies highlights potential therapeutic avenues to alleviate sepsis-induced organ dysfunction and improve patient outcomes.

Background: Intravascular bending, kinking, or fold-back deformation of an extracorporeal membrane oxygenation (ECMO) venous drainage cannula is a rare cannula-related event. Reports of such events are limited, and no mature or standardized management strategy has been established. We report a case of near-180° fold-back kinking of a venous drainage cannula in the inferior vena cava during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support, aiming to highlight the possibility of cannula deformation during cannulation and to provide a reference for individualized management of similar events. Case presentation: A 72-year-old woman with non-ST-segment elevation myocardial infarction complicated by refractory cardiogenic shock underwent right femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. After cannulation, bedside ultrasonography and radiography revealed near-180° fold-back kinking of the venous drainage cannula in the inferior vena cava. Because ECMO function remained stable and there was no evidence of vascular injury, bleeding, or thrombotic complications, the clinical team chose conservative observation under close monitoring. Seven days later, the patient was successfully weaned from VA-ECMO. Decannulation was uneventful, and no definite related adverse events were observed before discharge. Conclusion: During the placement of large-bore ECMO cannulas, premature withdrawal of the guidewire and obturator should be carefully avoided to prevent inadequate cannula support and subsequent deviation or fold-back kinking. For patients with fold-back kinking but stable cannula function and no evidence of vascular injury, bleeding, or thrombosis, conservative observation under close monitoring may be an individualized management option.