Suppression of mitochondrial complex I influences cell metastatic properties

PLoS One. 2013 Apr 22;8(4):e61677. doi: 10.1371/journal.pone.0061677. Print 2013.


Despite the fact that mitochondrial dysfunction has an important role in tumorigenesis and metastasis, the underlying mechanism remains to be elucidated. Mitochondrial Complex I (NADH:ubiquinone oxidoreductase) is the first and the largest protein complex of the mitochondrial electron-transport chain (ETC),which has an essential role in maintaining mitochondrial function and integrity. In this study, we separately knocked down two subunits of mitochondrial complex I, GRIM-19 or NDUFS3, and investigated their effects on metastatic behaviors and explored the possible mechanisms. Our data showed that stable down-modulation of GRIM-19 or NDUFS3 decreased complex I activity and reactive oxygen species (ROS) production; led to enhanced cell adhesion, migration, invasion, and spheroid formation; and influenced the expressions of extracellular matrix (ECM) molecules and its related proteins. We also observed that the expressions of GRIM-19, NDUFS3, and ECM elements were correlated with invasive capabilities of breast cancer cell lines. These results suggest that inhibition of complex I affects metastatic properties of cancer cells, and mitochondrial ROS might play a crucial role in these processes by regulating ECM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Cadherins / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Shape
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix / metabolism
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Integrins / metabolism
  • Mitochondria / enzymology
  • NADH Dehydrogenase / genetics*
  • NADH Dehydrogenase / metabolism
  • NADH, NADPH Oxidoreductases / genetics*
  • NADH, NADPH Oxidoreductases / metabolism
  • Neoplasm Metastasis*
  • Phenotype
  • RNA, Small Interfering / genetics
  • Reactive Oxygen Species / metabolism
  • Spheroids, Cellular


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • CDH2 protein, human
  • Cadherins
  • Cell Adhesion Molecules
  • Fibronectins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Integrins
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • NADH, NADPH Oxidoreductases
  • NDUFA13 protein, human
  • NADH Dehydrogenase
  • Electron Transport Complex I
  • NDUFS3 protein, human

Grants and funding

This work was supported by the Agency for Science, Technology and Research of Singapore and the supporting program of the Ministry of Human Resource of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.