The signaling mechanism through which deficitary mitochondrial function would activate nuclear genes required for mitochondrial biogenesis, has not been established. To explore the hypothesis that reactive oxygen species (ROS), a mitochondrial product, constitute part of the mitochondria-nuclei signaling pathway, we obtained HeLa cells depleted of mitochondrial DNA (p0 cells) through exposure to ethidium bromide. We found evidences of oxidative stress in p0 cells, employing a fluorescent probe and measuring NF-κB activation. Nuclear Respiratory Factor-1 (NRF-1) and Mitochondrial Transcription Factor A (Tfam) mRNA were measured by RT-PCR. For both transcription factors, p0 cells revealed significantly higher levels of mRNA. These results support several hypothesis: that endogenous ROS enhance the expression of nuclear mitochondrial biogenesis genes NRF-1 and Tfam; that DNA deprived mitochondria lead to cellular oxidative stress, probably because of incomplete biogenesis of the mitochondrial electron transport chain, and consequently, that ROS are part of a mitochondria-nuclei regulatory signaling pathway.
|Original language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Apr 29 1999|
Bibliographical noteFunding Information:
This work was supported by Grants FONDECYT 1960637 and PUC-PBMEC-98.