Donor lungs from donation after circulatory death (DCD) are an important supplementary source for expanding the donor pool in lung transplantation. Compared with donor lungs from donation after brain death (DBD), DCD donor lungs undergo hypoventilation, hypoxia, hypoperfusion, circulatory arrest, and functional warm ischemia after withdrawal of life-sustaining treatment. Consequently, varying degrees of pre-preservation injury may already be present before cold flushing and static hypothermic preservation and may further accumulate during preservation, rewarming, and reperfusion. Disruption of mitochondrial homeostasis may serve as a key link between these continuous injury phases and reperfusion vulnerability. The major mechanisms include impaired recovery of oxidative phosphorylation, metabolic reprogramming, increased reactive oxygen species generation, calcium dyshomeostasis, mitochondrial permeability transition pore opening, and dysregulation of mitochondrial dynamics and quality control. These alterations intersect with apoptosis, necroptosis, pyroptosis, ferroptosis, and other lytic cellular injury phenotypes. In recent years, controlled hypothermic storage at 10°C, ex vivo lung perfusion-based assessment and repair, optimization of procurement workflows, and metabolic interventions have provided new directions for DCD donor lung preservation and utilization. However, a substantial proportion of the available mechanistic evidence is derived from general donor lungs, marginal donor lungs, or models of lung ischemia-reperfusion injury and cannot be directly extrapolated to DCD lungs with different injury burdens. This review summarizes the continuous process of DCD donor lung preservation injury, mitochondrial homeostasis disruption, related cellular injury phenotypes, and preservation and dynamic assessment strategies. Evidence directly derived from DCD lungs is distinguished from lung transplantation-related evidence and cross-organ mechanistic references. These findings may inform donor-lung protection and optimization of lung transplantation workflows involving DCD donors.
