Figure 3.

Cellular and mitochondrial rewiring in different metabolic conditions. (a) Interaction of glucose and oxygen (O₂) with mitochondrial bioenergetics. In the cytosol, glucose is converted into pyruvate (Pyr), which is imported into mitochondria and converted into acetyl coenzyme A (AcCoA). AcCoA enters the tricarboxylic acid cycle (TCA) following a series of reactions that produce reducing equivalents, such as NADH and FADH₂. Electrons from redox equivalents are transported through the electron transport chain (ETC) in reactions coupled with the export of protons (H⁺) that contribute to the establishment of a pH and an electric gradient, resulting in a proton motive force that fuels the conversion of ADP into ATP by ATP synthase (not represented). Electrons (e⁻) that leak from the ETC may partially reduce O₂ into superoxide anion (O₂^.−), which may be converted into other more reactive oxygen species (ROS). GDH—glutamate dehydrogenase; Glu—glutamate; Gln—glutamine; GLS—glutaminase; HK—hexokinase; IDH—isocitrate dehydrogenase; IMM—inner mitochondrial membrane; IMS—intermembrane space; OGDH—oxoglutarate dehydrogenase; Lac—lactate; LDH—lactate dehydrogenase; MDH—malate dehydrogenase; PDH—pyruvate dehydrogenase; SDH—succinate dehydrogenase. Some elements used in this figure were obtained from smart.servier.com. (b) Metabolic remodeling induced by glucose (or its absence) and O₂ levels and its impact on energy production and redox system. Culturing cells in medium containing different glucose concentrations, in the presence of glutamine and pyruvate, and exposure to different O₂ levels have an impact on cellular responses. This emphasizes the importance of carefully controlling the cell culture medium and O₂ levels to obtain meaningful results from in vitro studies. For more details, see Section 4, Section 4.1, and Section 4.2.