Autophagy A Core Cellular Process with Emerging Links to Pulmonary Disease

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 08/2011; 184(11):1237-46. DOI: 10.1164/rccm.201106-0966CI
Source: PubMed


Autophagy is a highly conserved homeostatic pathway by which cells transport damaged proteins and organelles to lysosomes for degradation. Dysregulation of autophagy contributes to the pathogenesis of clinically important disorders in a variety of organ systems but, until recently, little was known about its relationship to diseases of the lung. However, there is now growing evidence at the basic research level that autophagy is linked to the pathogenesis of important pulmonary disorders such as chronic obstructive pulmonary disease, cystic fibrosis, and tuberculosis. In this review, we provide an introduction to the field of autophagy research geared to clinical and research pulmonologists. We focus on the best-studied autophagic mechanism, macroautophagy, and summarize studies that link the regulation of this pathway to pulmonary disease. Last, we offer our perspective on how a better understanding of macroautophagy might be used for designing novel therapies for pulmonary disorders.

7 Reads
  • Source
    • "Autophagy is a highly conserved homeostatic mechanism by which cells transport damaged proteins and organelles such as mitochondria to lysosomes for degradation in both health and disease conditions. It contributes to cellular homeostasis by (a) providing an alternative source of metabolic fuel, (b) removing damaged cellular components which are toxic to the cell such as dysfunctional mitochondria or aggregated proteins, and (c) promoting cell death [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Idiopathic pulmonary fibrosis is the most common and severe form of idiopathic interstitial pneumonias. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the pathogenesis remains elusive, and little therapeutic progress has been made in the last few years. Mortality in 3-5 years is still 50%. Autophagy, a highly conserved homeostatic mechanism necessary for cell survival, has been recently implicated in the pathogenesis of pulmonary disorders. In this paper we aim to highlight some key issues regarding the process of autophagy and its possible association with the pathogenesis of idiopathic pulmonary fibrosis.
    04/2013; 2013:420497. DOI:10.1155/2013/420497
  • Source
    • "Autophagy is a highly conserved process that helps in removing cellular debris emerging from normal homeostasis and from damage due to infection and inflammation [23]. Autophagy has been implicated in the elimination of Mtb by IFN-γ activated macrophages and has been shown to endow the autophagosomes of immune cells with antimicrobial activities [24,25]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Infection of humans with Mycobacterium tuberculosis (Mtb) results in latent tuberculosis infection (LTBI) in 90-95% of immune competent individuals, with no symptoms of active disease. The World Health Organization estimates that 1.5 billion people have LTBI, which can reactivate in the setting of waning host immunity, posing a threat to global TB control. Various animal models have been used to study the pathogenesis of TB. However, besides nonhuman primates, rabbits are the only animal model that fully recapitulates the pathological features of human TB, including progressive disease with necrosis and cavitation or establishment of spontaneous latency. Results We defined the molecular immunological correlates of LTBI establishment in a rabbit model of pulmonary infection with Mtb CDC1551. After aerosol infection, exponential bacterial growth was noted in the lungs for 4 weeks, followed by a significant decline by 12 weeks, resulting in the absence of cultivable bacilli by 24 weeks. We used rabbit whole genome microarrays to profile the lung transcriptome during the course of infection. At 2 weeks post-infection, gene networks involved in natural killer (NK) and dendritic cell (DC) activation and macrophage antimicrobial activities were highly upregulated. This was followed by upregulation of gene networks involved in macrophage and T cell activation and autophagy, peaking at 4 to 8 weeks. Concomitantly, host Th1, but not Th2 or inflammatory, immune response genes were significantly upregulated. Thus, the expression kinetics of genes involved in cross-talk between innate and adaptive immunity over the first 8 weeks post-infection were consistent with early efficient control of infection in the lungs. Interestingly, expression of many genes of the host innate and adaptive immune response pathways was downregulated at 12 weeks, suggesting that immune activation did not persist once bacilli began to clear from the infected lungs. Conclusions Our results suggest that early activation of host innate immunity prior to efficient activation of T cell-mediated adaptive immunity but not inflammation is essential for establishment of LTBI in Mtb CDC1551-infected rabbits. We also show that T cell activation and the host adaptive immune response networks are dampened once bacterial growth is controlled, ultimately resulting in spontaneous LTBI.
    Cell Communication and Signaling 02/2013; 11(1):16. DOI:10.1186/1478-811X-11-16 · 3.38 Impact Factor
  • Source
    Autophagy 11/2011; 7(11):1269-70. DOI:10.4161/auto.7.11.17941 · 11.75 Impact Factor
Show more


7 Reads
Available from