Background. The airway epithelium protects against inhaled noxious pollutants as it establishes a barrier between the external environment and underlying tissues. We have previously reported that this protective barrier is compromised in patient-derived COPD epithelium due to decreases in cofilin 1 with increases in actin polymer mass (PMID: 35118497). Cofilin 1 is also implicated in mitochondrial function and shown to regulate mitochondrial fission.
Aim. To determine if loss of cofilin 1 in COPD airway epithelium alters the mitochondrial structure, biogenesis, and energetics.
Methods. Airway epithelial cells from normal and COPD donors were differentiated on the air-liquid interface for 4 to 6 weeks. cofilin 1 was knocked down from normal epithelium using adeno-CFL1shRNA, overexpressed in COPD epithelium using adeno-CFL1, and was assessed for mitochondrial structure (MitoTracker Green), biogenesis (PGC1a), energetics (Seahorse XF24 extracellular flux analyzer), and mitochondrial fission (DRP1).
Results. Our data indicate that both COPD epithelium and knockdown of cofilin 1 in normal epithelium did not alter mitochondrial structure but significantly decreased mitochondrial oxygen consumption rate and biogenesis with an increase in fission markers compared to normal cells.

Conclusion. This implies cytoskeletal rearrangements in COPD decrease mitochondrial function, and strategies to target the cytoskeleton can improve epithelial health.