Metabolic Plasticity of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is one of the most common and life-threatening leukemias. A highly diverse and flexible metabolism contributes to the aggressiveness of the disease that is still difficult to treat. By using different sources of nutrients for energy and biomass supply, AML cells gain metabolic plasticity and rapidly outcompete normal hematopoietic cells. This review aims to decipher the diverse metabolic strategies and the underlying oncogenic and environmental changes that sustain continuous growth, mediate redox homeostasis and induce drug resistance in AML. We revisit Warburg's hypothesis and illustrate the role of glucose as a provider of cellular building blocks rather than as a supplier of the tricarboxylic acid (TCA) cycle for energy production. We discuss how the diversity of fuels for the TCA cycle, including glutamine and fatty acids, contributes to the metabolic plasticity of the disease and highlight the roles of amino acids and lipids in AML metabolism. Furthermore, we point out the potential of the different metabolic effectors to be used as novel therapeutic targets.

The nucleus-encoded protein MOC1 is essential for mitochondrial light acclimation in Chlamydomonas reinhardtii.

Mitochondrial respiration plays an important role in optimizing photosynthetic efficiency in plants. As yet, the mechanisms by which plant mitochondria sense and respond to changes in the environment are unclear, particularly when exposed to light. Here we describe the characterization of the Chlamydomonas reinhardtii mutant stm6, which was identified on the basis of impaired state transitions, a mechanism that regulates light harvesting in the chloroplast. The gene disrupted in stm6, termed Moc1, encodes a homologue of the human mitochondrial transcription termination factor (mTERF). MOC1 is targeted to the mitochondrion, and its expression is up-regulated in response to light. Loss of MOC1 causes a high light-sensitive phenotype and disrupts the transcription and expression profiles of the mitochondrial respiratory complexes causing, as compared with wild type, light-mediated changes in the expression levels of nuclear and mitochondrial encoded cytochrome c oxidase subunits and ubiquinone-NAD subunits. The absence of MOC1 leads to a reduction in the levels of cytochrome c oxidase and of rotenone-insensitive external NADPH dehydrogenase activities of the mitochondrial respiratory electron transfer chain. Overall, we have identified a novel mitochondrial factor that regulates the composition of the mitochondrial respiratory chain in the light so that it can act as an effective sink for reductant produced by the chloroplast.