[Abstract unavailable

Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.

Macroautophagy (hereafter autophagy), literally defined as a type of self-eating, is a dynamic cellular process in which cytoplasm is sequestered within a unique compartment termed the phagophore. Upon completion, the phagophore matures into a double-membrane autophagosome that fuses with the lysosome or vacuole, allowing degradation of the cargo. Nonselective autophagy is primarily a cytoprotective response to various types of stress; however, the process can also be highly selective. Autophagy is involved in various aspects of cell physiology, and its dysregulation is associated with a range of diseases. The regulation of autophagy is complex, and the process must be properly modulated to maintain cellular homeostasis. In this review, we focus on the current state of knowledge concerning transcriptional, post-transcriptional, and post-translational regulation of autophagy in yeast and mammals.

The study aimed to compare the reported oncological outcomes based on satisfactory lymph node dissection (LND) or lymph node sampling (LNS), systemic and loco-regional recurrence rate and long-term survival rate of patients with early-stage non-small-cell lung cancer (NSCLC) who underwent video-assisted thoracic surgery (VATS) lobectomy or thoracotomy lobectomy. A systematic review was conducted using PubMed, EMBASE and OVID-EBMR databases ranging from 1990 to 2011. The studies compared VATS and thoracotomy for patients with NSCLC, with results including LND or LNS where recurrence as well as survival rates were identified. Data were abstracted by two reviewers independently. Mean difference or risk ratio (RR) were pooled using RevMan 5.0 statistical software. 5389 cases were included, of which 2380 underwent VATS and 3009 underwent thoracotomy. There was no significant difference in the number of total LND or LNS procedures (MD: -0.63; 95% confidence intervals (95% CI): -1.47 to 0.21; P = 0.14) or mediastinal LND or LNS (MD: -0.51; 95% CI: -1.58 to 0.56; P = 0.35) between the two groups. Systemic (RR: 0.61; 95% CI: 0.48 to 0.78; P < 0.01) and loco-regional (RR: 0.66; 95% CI: 0.46 to 0.95; P = 0.03) recurrence rates were significantly lower in the VATS group. Moreover, a significantly higher survival rate (RR: 1.09; 95% CI: 1.03 to 1.15; P < 0.01) was also demonstrated by a Forest plot in the VATS group. These results suggest that VATS lobectomy might be an eligible alternative in place of thoracotomy in patients with early-stage NSCLC by reducing recurrence and improving survival rates.

Macroautophagy (hereafter autophagy) is one of the major degradation systems in eukaryotic cells, and its dysfunction may result in diseases ranging from neurodegeneration to cancer. Although most of the autophagy-related (Atg) proteins that function in this pathway were first identified in yeast, many were subsequently shown to have homologs in higher eukaryotes including humans, and the overall mechanism of autophagy is highly conserved. The most prominent feature of autophagy is the formation of a double-membrane sequestering compartment, the phagophore; this transient organelle surrounds part of the cytoplasm and matures into an autophagosome, which subsequently fuses with the vacuole or lysosome to allow degradation of the cargo. Much attention has focused on the process involved in phagophore nucleation and expansion, but many questions remain. Here, we identified the yeast protein Icy2, which we now name Atg41, as playing a role in autophagosome formation. Atg41 interacts with the transmembrane protein Atg9, a key component involved in autophagosome biogenesis, and both proteins display a similar localization profile. Under autophagy-inducing conditions the expression level of Atg41 increases dramatically and is regulated by the transcription factor Gcn4. This work provides further insight into the mechanism of Atg9 function and the dynamics of sequestering membrane formation during autophagy.