title: Cross-talk between apoptosis and autophagy in lung epithelial cell death.
abstract: As an essential organ for gas exchange, the lungs are constantly exposed to the external environment and are simulated by toxicants and pathogens. The integrity of lung epithelium and epithelial cells is crucial for fulfilling the physiological functions of the lung. The homeostasis of lung epithelial cells is maintained by a complex network by which survival and death are tightly regulated. Upon noxious stimulation, lung epithelium attempts to maintain its normal structure and function. Savage of injured cells and clearance of unsalvageable dying cells or unwanted proliferated cells constantly occur in the lung epithelium. Apoptosis, or programmed cell death, functions as a primary mechanism to discard unsalvageable cells or unwanted overgrowth. Autophagy, on the other hand, initially attempts to save and repair the injured cells. However, when the noxious stimulation is too strong and cell survival becomes unfeasible, autophagy behaves oppositely and cooperates with apoptosis, subsequently accelerates cell death. The imbalance between autophagy and apoptosis potentially leads to tumorigenesis or devastating cell death/lung injury. Therefore, the cross-talk between apoptosis and autophagy in lung epithelial cells is critical in determining the fate of epithelial cells and its balance of death/survival in response to environmental stimuli. In this review, we will focus on the current understandings of the communications between apoptosis and autophagy in lung epithelial cells. We will review multiple key regulators and their underlying mechanisms involved in the cross-talk between apoptosis and autophagy. The autophagic factors, such as the Beclin-1, ATG5, Fap-1, p62 and concentration-dependent LC3B, all closely interact with multiple apoptosis pathways. Understanding these regulations of apoptosis/autophagy cross-talk potentially provides novel targets for developing diagnostic and therapeutic strategies for many lung diseases, including lung injuries and malignancies.
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115.
authors.forename: Hyung-Geun
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115.
authors.forename: Sukrutha
authors.initials: S
authors.lastname: Chettimada
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jin
keywords: apoptosis; autophagy; epithelial cell; lung TBC1D4