Mitochondria at the frontline of environmental toxicity in conflict and crisis zones: mechanisms, models, and countermeasures

• Complex toxicants from conflict environments trigger mitochondrial dysfunction. • Mitochondria integrate oxidative, metabolic, and apoptotic stress responses. • Combined nanoparticle-radiation exposures converge on mitochondrial injury. • Advanced 3D lung models enable mechanistic and therapeutic investigation. • Targeting mitochondrial resilience offers new countermeasure opportunities. Populations exposed to conflict and crisis zones - including military personnel, first responders, and civilians - face complex environmental stressors such as combustion-derived irritants, engineered nanoparticles, and ionizing radiation. Mitochondria, as central regulators of cellular bioenergetics and oxidative stress, are highly susceptible to these exposures. This review examines two key scenarios: (i) inhaled respiratory toxicants and (ii) radio-combined exposures involving nanoparticles and ionizing radiation. Both conditions converge on mitochondrial dysfunction, causing oxidative damage, disrupted energy metabolism, and long-term tissue impairment. We discuss how advanced 3D lung models and mitochondrial flux analyses provide mechanistic insight and enable the identification of mitochondria-targeted countermeasures, including antioxidants, biogenesis activators, and nanotherapeutics. In conflict and technological crisis settings, addressing mitochondrial vulnerability represents a pivotal opportunity to prevent chronic toxicity and reinforce physiological resilience across both military and civilian populations.