Mitochondrial biogenesis in the liver during development and oncogenesis.
The analysis of the expression of oxidative phosphorylation genes in the liver during development reveals the existence of two biological programs involved in the biogenesis of mitochondria. Differentiation is a short-term program of biogenesis that is controlled at post-transcriptional levels of gene expression and is responsible for the rapid changes in the bioenergetic phenotype of mitochondria. In contrast, proliferation is a long-term program controlled both at the transcriptional and post-transcriptional levels of gene expression and is responsible for the increase in mitochondrial mass in the hepatocyte. Recently, a specific subcellular structure involved in the localization and control of the translation of the mRNA encoding the beta-catalytic subunit of the H(+)-ATP synthase (beta-mRNA) has been identified. It is suggested that this structure plays a prominent role in the control of mitochondrial biogenesis at post-transcriptional levels. The fetal liver has many phenotypic manifestations in common with highly glycolytic tumor cells. In addition, both have a low mitochondrial content despite a paradoxical increase in the cellular representation of oxidative phosphorylation transcripts. Based on the paradigm provided by the fetal liver we hypothesize that the aberrant mitochondrial phenotype of fast-growing hepatomas represents a reversion to a fetal program of expression of oxidative phosphorylation genes by the activation, or increased expression, of an inhibitor of beta-mRNA translation.
Cuezva
J M
JM
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
Ostronoff
L K
LK
Ricart
J
J
López de Heredia
M
M
Di Liegro
C M
CM
Izquierdo
J M
JM
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D008099:Liver / Q000254:growth & development / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D006180:Proton-Translocating ATPases / Q000235:genetics
D006180:Proton-Translocating ATPases