Activated heme synthesis regulates glycolysis and oxidative metabolism in breast and ovarian cancer cells.

Heme is an essential cofactor for enzymes of the electron transport chain (ETC) and ATP synthesis in mitochondrial oxidative phosphorylation (OXPHOS). Heme also binds to and destabilizes Bach1, a transcription regulator that controls expression of several groups of genes important for glycolysis, ETC, and metastasis of cancer cells. Heme synthesis can thus affect pathways through which cells generate energy and precursors for anabolism.

Replication stress inhibits synthesis of histone mRNAs in yeast by removing Spt10p and Spt21p from the histone promoters.

Proliferating cells coordinate histone and DNA synthesis to maintain correct stoichiometry for chromatin assembly. Histone mRNA levels must be repressed when DNA replication is inhibited to prevent toxicity and genome instability due to free non-chromatinized histone proteins. In mammalian cells, replication stress triggers degradation of histone mRNAs, but it is unclear if this mechanism is conserved from other species.

Probing Metabolic Changes in IFNγ-Treated Ovarian Cancer Cells.

Interferon-γ (IFNγ) is a pleiotropic cytokine that signals to many different cell types. IFNγ has both antitumor functions and pro-tumorigenic effects and regulates different aspects of cell physiology, including metabolism. Cancer cells undergo a complex rearrangement of metabolic pathways that allows them to satisfy the needs of increased proliferation, and many cancer cells redirect glucose metabolism from oxidative phosphorylation to aerobic glycolysis.

DNA damage response activates respiration and thereby enlarges dNTP pools to promote cell survival in budding yeast.

The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Previously, we found that decreased histone expression induces mitochondrial respiration, raising the question whether the DDR also stimulates respiration. Here, using oxygen consumption and ATP assays, RT-qPCR and ChIP-qPCR methods, and dNTP analyses, we show that DDR activation in the budding yeast , either by genetic manipulation or by growth in the presence of genotoxic chemicals, induces respiration.

Reciprocal Regulation of AMPK/SNF1 and Protein Acetylation.

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) serves as an energy sensor and master regulator of metabolism. In general, AMPK inhibits anabolism to minimize energy consumption and activates catabolism to increase ATP production. One of the mechanisms employed by AMPK to regulate metabolism is protein acetylation.

Metformin as an Anticancer Agent.

Metformin has been a frontline therapy for type 2 diabetes (T2D) for many years. Its effectiveness in T2D treatment is mostly attributed to its suppression of hepatic gluconeogenesis; however, the mechanistic aspects of metformin action remain elusive. In addition to its glucose-lowering effect, metformin possesses other pleiotropic health-promoting effects that include reduced cancer risk and tumorigenesis.