Excitotoxicity is likely to occur in pathological scenarios in which mitochondrial function is already compromised, shaping neuronal responses to glutamate. In fact, mitochondria sustain cell bioenergetics, tune intracellular Ca²⁺ dynamics, and regulate glutamate availability by using it as metabolic substrate. Here, we suggest the need to explore glutamate toxicity in the context of specific disease models in which it may occur, re-evaluating the impact of mitochondrial dysfunction on glutamate excitotoxicity. Our aim is to signpost new approaches, perhaps combining glutamate and pathways to rescue mitochondrial function, as therapeutic targets in neurological disorders.

在线粒体功能已经受损的病理情况下，可能会发生兴奋性毒性，从而影响神经元对谷氨酸的反应。事实上，线粒体维持细胞生物能学，调节细胞内 Ca ²⁺动力学，并通过将其用作代谢底物来调节谷氨酸的可用性。在这里，我们建议需要在可能发生的特定疾病模型的背景下探索谷氨酸毒性，重新评估线粒体功能障碍对谷氨酸兴奋性毒性的影响。我们的目标是标出新的方法，或许结合谷氨酸盐和途径来拯救线粒体功能，作为神经系统疾病的治疗靶点。