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 m itochondria. Mitochondria contain their own DNA genome encoding 13 polypept ides that combine with nuclear-derived subunits to create functional enzyme complexes of the electron transport chain. Therefore, coordination of mito chondrial and nuclear transcription is necessary to achieve a sustained ele vation in mitochondrial ATP production. Pre-B-lymphocytes stimulated with l ipopolysaccharide exhibit increased activity levels of the mitochondrial en zymes, succinate dehydrogenase and cytochrome c oxidase. Immunoblot analyse s of purified mitochondria indicate an increase in the mitochondrial transc ription factor (mtTFA) levels in mitochondria induced by cell stimulation. This increase is consistent with increased mtTFA production in the cytoplas m. In addition, mitochondrial protein extracts indicate an increase in prot ein binding to a mtTFA-DNA binding site from the mitochondrial genome, subs equent to cell stimulation. These results indicate that mitochondrial activ ity changes during B-lymphocyte stimulation, and mtTFA may contribute to th e coordination of respiration with cellular energy demand. (C) 2000 Elsevie r Science B.V. All rights reserved.