Lung cancer is the leading cause of cancer-related death in the United States, and more than 150,000 Americans die of lung cancer each year. Despite our best treatment, efforts to cure lung cancer have failed in most cases, partly due to an insufficient understanding of the biology of metastasis, which almost inevitably leads to lung cancer death. Therefore, understanding better the mechanism regulating metastasis will allow us to gain deeper insights into the disease basis, on which novel therapeutic strategies for treating metastatic lung cancer can be developed and tested. On the basis of our preliminary studies, we posit that an autophagy related gene plays a critical role in the regulation of lung cancer metastasis through a novel mitochondria associated mechanism. The primary objectives of this proposal are to determine whether manipulating the expression of this gene or its mitochondria associated function can inhibit the dissemination of lung cancer. As such, our studies not only reveal a new basic mechanism for lung cancer, but have translational potentials. Because there are about 2 million new lung cancer cases each year globally (World Health Organization statistics), our studies may have a major impact on public health.