A. Brent Carter, MD, received his medical degree at the University of Missouri. His post-graduate training as a resident in internal medicine and as a fellow in pulmonary and critical care medicine was completed at the University of Iowa Carver College of Medicine. Dr. Carter became a professor in Internal Medicine at the University of Iowa. He is now a professor in medicine and Scientific Director of the Interstitial Lung Disease Program at UAB.

Dr. Carter’s research interests are related to the regulation of inflammatory and fibrotic responses that occur in the lung in environmental lung injury and pulmonary fibrosis. Dr. Carter’s studies include investigations to understand the role of mitochondrial bioenergetics and mitochondrial turnover and biogenesis have in modulating the phenotype of alveolar macrophages. The studies suggest that the phenotype of alveolar macrophages is a critical regulator of fibrotic responses in the lung. 


Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder with increasing incidence. Mitochondrial oxidative stress in alveolar macrophages is directly linked to pulmonary fibrosis. Mitophagy, the selective engulfment of dysfunctional mitochondria by autophagasomes, is important for cellular homeostasis and can be induced by mitochondrial oxidative stress. Here, we show Akt1 induced macrophage mitochondrial reactive oxygen species (ROS) and mitophagy. Mice harboring a conditional deletion of Akt1 in macrophages (Akt1(-/-)Lyz2-cre) and Park2(-/-) mice had impaired mitophagy and reduced active transforming growth factor-β1 (TGF-β1). Although Akt1 increased TGF-β1 expression, mitophagy inhibition in Akt1-overexpressing macrophages abrogated TGF-β1 expression and fibroblast differentiation. Importantly, conditional Akt1(-/-)Lyz2-cre mice and Park2(-/-) mice had increased macrophage apoptosis and were protected from pulmonary fibrosis. Moreover, IPF alveolar macrophages had evidence of increased mitophagy and displayed apoptosis resistance. These observations suggest that Akt1-mediated mitophagy contributes to alveolar macrophage apoptosis resistance and is required for pulmonary fibrosis development.

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