Emphysema is caused by smoking and secondhand smoking. How emphysema develops is still not well understood. Emphysema is characterized by lung tissue destruction and death of cells in the alveoli (air sacs). Alveolar cells play an important role in lung tissue repair after injury. We have found that emphysema patients exhibit higher DNA damage in mitochondria, the microscopic power plants, inside alveolar cells. This damaged DNA contributes to cell death. We will study the mechanism of mitochondrial DNA damage in alveolar cells to determine whether a protein called XLF, which is involved in mitochondrial DNA damage repair, protects cells against this disease development and can serve as a novel therapeutic target. Targeting XLF can provide a new strategy to repair alveolar cells and slow down the development of emphysema.