Alterations in mitochondria and mtTFA in response to LPS-induced differentiation of B-cells.

Stimulation of immune cells results in altered cell function and metabolism, which must be recognized by and coordinated with energy production from mitochondria. Mitochondria contain their own DNA genome encoding 13 polypeptides that combine with nuclear-derived subunits to create functional enzyme complexes of the electron transport chain. Therefore, coordination of mitochondrial and nuclear transcription is necessary to achieve a sustained elevation in mitochondrial ATP production. Pre-B-lymphocytes stimulated with lipopolysaccharide exhibit increased activity levels of the mitochondrial enzymes, succinate dehydrogenase and cytochrome c oxidase. Immunoblot analyses of purified mitochondria indicate an increase in the mitochondrial transcription factor (mtTFA) levels in mitochondria induced by cell stimulation. This increase is consistent with increased mtTFA production in the cytoplasm. In addition, mitochondrial protein extracts indicate an increase in protein binding to a mtTFA-DNA binding site from the mitochondrial genome, subsequent to cell stimulation. These results indicate that mitochondrial activity changes during B-lymphocyte stimulation, and mtTFA may contribute to the coordination of respiration with cellular energy demand.