Abstract (242 words) Mitochondrial damage is often overlooked in acute lung injury (ALI), but most of the lung's physiological processes, such as airway tone, muco-ciliary clearance, Va/Q matching, and immune surveillance require aerobic energy provision. Because the cell's processes of mitochondrial quality control (QC) regulate the elimination and replacement of damaged mitochondria to support cell survival, we evaluated mitochondrial biogenesis and mitophagy in the alveolar region of mice in a validated S. aureus pneumonia model. We report that apart from cell lysis by direct contact with microbes, extensive oxidative mitochondrial damage was detected along with epithelial cell death. Cell death by TUNEL staining occurred on days 1 and 2 post-inoculation: apoptosis shown by caspase 3 cleavage was present on days 1 and 2, while necroptosis shown by increased levels of phospho-MLKL and RIPK1 was present on day 1. Cell death in alveolar type I (AT1) cells assessed by BAL fluid RAGE levels was high post-inoculation, yet in AT2 cells, induction of both mitochondrial biogenesis and mitophagy occurred. These alveolar mitochondrial QC mechanisms were evaluated by locating increases in citrate synthase content, nuclear localization of mitochondrial biogenesis regulators NRF-1 and PGC-1α and increased LC3II/LC3I ratios in AT2 cells. Concomitantly, p62, Pink 1, and Parkin proteins were up-regulated, indicating mitophagy. By confocal microscopy, mitochondrial biogenesis and mitophagy was often observed within the same cells on the first day. These findings imply that activation of mitochondrial QC programs in damaged AT2 cells promotes cell survival to support return of alveolar function.