Recent Advances in Metabolism and Oxidative Stress in Human Diseases

Dear Colleagues,

Metabolism, the series of reactions that occur in living cells, involves many interconnected cellular pathways that ultimately provide cells with chemical energy in the form of ATP. Most of the cell ATP is produced by mitochondrial oxidative phosphorylation (OxPhos). In turn, the OxPhos efficacy seems to depend on the mitochondrial morphology and number, which likely reflect the metabolic needs of the cell. Mitochondria are dynamic organelles that divide and fuse to form an extensive network. Moreover, recent evidence points to the existence of a connection of the mitochondrial reticulum to the endoplasmic reticulum. Moreover, in the recent years an ectopic OxPhos activity has been described in membranes other than mitochondrial membranes, such as the rod outer segments, the myelin sheath, and the plasma membranes of hepatocytes, cancer and endothelial cells, as well as exosomes, microvesicles and platelets. Mitochondria also play a role in Ca²⁺ buffering and are the main intracellular sources of reactive oxygen species (ROS), a by-product of oxidative phosphorylation under physiological conditions. Oxidative stress, defined as an imbalance between ROS generation and the endogenous and exogenous antioxidant systems, is emerging as the ultimate cause of several diverse diseases. Oxidative stress is involved in the ageing process and multiple age-related diseases, such as atherosclerosis, cardiovascular diseases (CVDs), and neurodegenerative diseases. Platelets contribute to inflammation and immune responses, and play an important role in cardiovascular disease thrombosis and atherosclerosis. A link exists between Alzheimer’s disease and dysfunctional glucose metabolism. Metabolic reprogramming leads to cellular senescence. Metabolism is profoundly altered in osteoarthritis (OA). The metabolic reprogramming of most core metabolic pathways, including glucose, glutamine, amino acids, and lipids, is a hallmark of cancer cells in the various stages of the disease. The metabolic switch of cancer cells from aerobic glycolysis (Warburg effect) to OxPhos is characteristic of the acquisition of metastasizing features. Endothelial cell metabolism is important in both health and disease, being a determinant of angiogenesis—a process also involved in cancer growth. Metabolic pathways are recognized as important regulators of immune activation, also influencing the development of autoimmune diseases. ROS generation promotes the activation of the mechanistic target of rapamycin (mTOR), in turn a metabolic sensor. Understanding the mechanisms of metabolic reprogramming, thereby including mitochondrial function and biology, has the potential to lead to the development of effective treatments for a number of diseases.

Dr. Isabella Panfoli
Guest Editor

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