Mitochondria respond differentially to brain damage, and these mechanisms may be important during acute inflammation and for repair during the post-injury period. At basal levels, the expression of cytokines and chemokines are different in men vs women’s brain, and so is the production of oxidative stress coupled with the mitochondrial membrane potential and the mitochondrial permeability transition pore. Interestingly, the activity/expression of some mitochondrial complexes of the electron transport chain are more expressed in women, and this raises the hypothesis that endogenous hormones may be playing a role in promoting said mitochondrial activity. By inducing early menopause in animals (ovariectomy and orchidectomy) and cells (siRNA aromatase) there is a shift in lipid metabolism and this is reflected on how mitochondria respond to metabolic damage. A large part of these effects may be related to the expression of neuroglobin, a cytosolic protein, but which, in the face of brain trauma, is transported to mitochondria where it interacts with Complex I and, mostly Complex III, and proteins such as cyc1, ETFDH/Q/ETFA and p32/c1qbp complexes, thus regulating apoptotic mechanisms, oxidative phosphorylation, mitochondrial immunometabolism, and these are all different depending on the sex. In this talk, we will discuss these mitochondrial mechanisms responsible for a response to metabolic damage, emphasizing how the female mitochondria respond differently compared to males.