Autophagy Is Required for Mitochondrial Function, Lipid Metabolism, Growth, and Fate of KRAS(G12D)-driven Lung Tumors

Autophagy. 2013 Oct;9(10):1636-8. doi: 10.4161/auto.26123. Epub 2013 Aug 15.


Evidence suggests that the role of autophagy in tumorigenesis is context dependent. Using genetically engineered mouse models (GEMMs) for human non-small-cell lung cancer (NSCLC), we found that deletion of the essential autophagy gene, Atg7, in KRAS(G12D)-driven NSCLC inhibits tumor growth and converts adenomas and adenocarcinomas to benign oncocytomas characterized by the accumulation of respiration-defective mitochondria. Atg7 is required to preserve mitochondrial fatty acid oxidation (FAO) to maintain lipid homeostasis upon additional loss of Trp53 in NSCLC. Furthermore, cell lines derived from autophagy-deficient tumors depend on glutamine to survive starvation. This suggests that autophagy is essential for the metabolism, growth, and fate of NSCLC.

Keywords: KRAS; NSCLC; autophagy; fatty acid oxidation; metabolism; mitochondria; oncocytoma; p53.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / physiology*
  • Cell Proliferation / physiology
  • Humans
  • Lipid Metabolism / physiology*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mitochondria / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics
  • ras Proteins / metabolism*


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins