TY - JOUR
T1 - Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells
AU - Miranda, Soledad
AU - Foncea, Rocio
AU - Guerrero, Javier
AU - Leighton, Federico
N1 - Funding Information:
This work was supported by Grants FONDECYT 1960637 and PUC-PBMEC-98.
PY - 1999/4/29
Y1 - 1999/4/29
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1999.0580
DO - 10.1006/bbrc.1999.0580
M3 - Article
C2 - 10222232
AN - SCOPUS:0033614441
SN - 0006-291X
VL - 258
SP - 44
EP - 49
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -