Functional characterization of the promoter of the human Lon protease gene

Mitochondrion. 2011 Jan;11(1):200-6. doi: 10.1016/j.mito.2010.09.010. Epub 2010 Oct 7.

Abstract

Lon, a nuclear-encoded mitochondrial enzyme, degrades oxidized proteins of the mitochondrial (mt) matrix, and participates in the replication of mtDNA. Lon is upregulated in the presence of substances such as stavudine (d4T), D-deoxyribose (dRib), that increase the intracellular reactive oxygen species (ROS) levels, or in the presence of H(2)O(2.) Here we show the promoter region -623/+1 is essential for response to ROS, and that in SW872, HepG2 and WI-38 cell lines the region -1230/-623 represses transcription, while the region -2023/-1230 increases promoter activity. D4T upregulates Lon promoter activity in all cell lines while dRib upregulates Lon mainly in HepG2 cells, and in shorter incubation times. These data confirm that Lon can be considered a stress responsive protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Replication
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Deoxyribose / pharmacology
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Heat-Shock Response*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Oxidative Stress*
  • Promoter Regions, Genetic / genetics*
  • Protease La / genetics
  • Protease La / metabolism*
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology
  • Stavudine / pharmacology
  • Up-Regulation*

Substances

  • DNA, Mitochondrial
  • Heat-Shock Proteins
  • Reactive Oxygen Species
  • Deoxyribose
  • Hydrogen Peroxide
  • Stavudine
  • Protease La