MDM2 and mitochondrial function: One complex intersection

Biochem Pharmacol. 2019 Apr:162:14-20. doi: 10.1016/j.bcp.2018.10.032. Epub 2018 Nov 1.

Abstract

Decades of research reveal that MDM2 participates in cellular processes ranging from macro-molecular metabolism to cancer signaling mechanisms. Two recent studies uncovered a new role for MDM2 in mitochondrial bioenergetics. Through the negative regulation of NDUFS1 (NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1) and MT-ND6 (NADH dehydrogenase 6), MDM2 decreases the function and efficiency of Complex I (CI). These observations propose several important questions: (1) Where does MDM2 affect CI activity? (2) What are the cellular consequences of MDM2-mediated regulation of CI? (3) What are the physiological implications of these interactions? Here, we will address these questions and position these observations within the MDM2 literature.

Keywords: Apoptosis; Bioenergetics; Complex I; Electron transport chain; MDM2; Mitochondria; Oncogene; Tumor suppressor; p53.

Publication types

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

MeSH terms

  • Animals
  • Energy Metabolism / physiology
  • Humans
  • Mitochondria / physiology*
  • Protein Binding / physiology
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Proto-Oncogene Proteins c-mdm2 / metabolism*

Substances

  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2