Brain bioenergetics and cognition: beyond simple energy
Juan Pedro Bolaños
IBFG – (Universidad de Salamanca-CSIC)
Different brain cell types exhibit distinctive metabolic characteristics that link energy economy to cellular function. Astrocytes and neurons, for example, differ dramatically in their reliance on glycolysis versus oxidative phosphorylation, underscoring that fuel metabolic efficiency is not uniform across cell types. A key factor shaping this divergence is the structural organization of the mitochondrial respiratory chain into supercomplexes. Specifically, complexes I (CI) and III (CIII) form a CI-CIII supercomplex, but the degree of this assembly varies by cell type. In neurons, CI is predominantly assembled into supercomplexes, resulting in highly efficient mitochondrial respiration and minimal reactive oxygen species (ROS) generation. In contrast, in astrocytes, a larger fraction of CI remains unassembled, existing freely apart from CIII, leading to lower respiratory efficiency and increased mitochondrial ROS production. Despite this apparent inefficiency, astrocytes exhibit a highly adaptable metabolism capable of responding to diverse stressors. Their more flexible CI-CIII organization enables flexible ROS signaling, which activates antioxidant programs through transcription factors such as Nrf2. This modular architecture allows astrocytes not only to balance energy production but also to support neuronal health and influence complex organismal behaviors.