Thus, our findings offer a new insight into the role of HO-1 in attenuating oxidative stress through the mitochondrial fusion protein Mfn1, which greatly contributes to further clarification of the mechanism of HO-1 protection against oxidative stress and provides opportunities for designing mitochondria-targeted HO-1 interventions for ALI/ARDS treatment. Here, HMOX1 is linked to acute respiratory distress syndrome.