- Under conditions of high nutrient availability and low ATP synthesis, mitochondria generate reactive oxygen species (ROS) that must be removed to avoid cell injury. Among the enzymes involved in this scavenging process, peroxidases play a crucial role, using NADPH provided mostly by nicotinamide nucleotide transhydrogenase (NNT). However, scarce information is available on how and to what extent ROS formation is linked to mitochondrial oxygen consumption. A new study by Smith et al. shows that NNT activity maintains low ROS levels by means of a fine modulation of mitochondrial oxygen utilization.
- Carnitine, a molecule found in red meat, is metabolized to trimethylamine (TMA) by the gut microbiota. TMA is then converted in the liver to trimethylamine oxide, a causative agent for atherosclerosis. Kountz et al. have discovered an alternative pathway for carnitine metabolism in the gut bacterium Eubacterium limosum. Instead of forming TMA, carnitine is demethylated by the newly discovered methyltransferase MtcB, sending one-carbon units into production of short-chain fatty acids. These results suggest that bacterial metabolic activities could promote cardiovascular health by preventing the buildup of toxin precursors.
- Lipid droplets (LDs) are key lipid storage structures in cells. One might think that they simply result from lipid molecules separating out within the aqueous intracellular environment. However, closer investigation has revealed that LDs are well-organized organelles surrounded by proteins that tightly control lipid entry into and exit from these organelles.
- Macromolecules such as proteins, lipids, and carbohydrates often have complex structures that underpin their cellular functions. The sugar alcohol myo-inositol is a notable exception—its simple six-carbon structure is rather unremarkable (Fig. 1) but is used in countless cellular processes in all domains of life (1).
- Triple-negative breast cancer (TNBC) is characterized by its aggressive biology, early metastatic spread, and poor survival outcomes. TNBC lacks expression of the targetable receptors found in other breast cancer subtypes, mandating use of cytotoxic chemotherapy. However, resistance to chemotherapy is a significant problem, encountered in about two-thirds of TNBC patients, and new strategies are needed to mitigate resistance. In this issue of the Journal of Biological Chemistry, Geck et al. report that TNBC cells are highly sensitive to inhibition of the de novo polyamine synthesis pathway and that inhibition of this pathway sensitizes cells to TNBC-relevant chemotherapy, uncovering new opportunities for addressing chemoresistance.
- The enzyme lipoprotein lipase (LPL) is responsible for breaking down triglycerides in the blood. Mutations in LPL cause a rare but debilitating disorder characterized by excessive plasma triglyceride levels for which treatment options are limited. Nimonkar et al. now present a fusion protein between LPL and its physiological transporter GBIHBP1 that is highly active and largely resistant to physiological inhibitors of LPL. Injecting this fusion protein effectively lowers plasma triglycerides in mice and represents a promising new approach for lowering triglycerides in patients with familial chylomicronemia syndrome.
- Lysine polyphosphorylation (K-PPn) is a relatively new post-translational modification, the full targets and functional consequences of which are unknown. A critical problem in the study of endogenous K-PPn of proteins in the yeast model system is that its nonenzymatic nature and its susceptibility to polyphosphatases make it potentially susceptible to artifacts during extraction. A new study confirms that K-PPn modifications can be altered during sample handling, provides new insights into the mechanism of K-PPn, and develops a yeast model strain, devoid of both vacuolar polyP and polyphosphatases, that allows detection of authentic endogenous K-PPn.
- Healthy cells are expert recyclers, rapidly breaking down worn-out or surplus macromolecules and reusing their building blocks. Several pathways, such as the proteasomal degradation route for protein breakdown, specifically pick out damaged or expendable molecules.
- The discovery in 1959 that metformin (dimethylbiguanide) lowers blood glucose levels in people with type 2 diabetes (1) has been a major boon for millions with this common metabolic disorder. Metformin is currently also being studied as a therapeutic agent for managing other serious maladies, such as fatty liver disease, cardiovascular disorders, and cancer.