Aluminum-induced Defective Mitochondrial Metabolism Perturbs Cytoskeletal Dynamics in Human Astrocytoma Cells

Although aluminum (AI), a known environmental toxin, has been implicated in a variety of neurological disorders, the molecular mechanism responsible for these conditions is not fully understood. In this report, we demonstrate the ability of AI to trigger mitochondrial dysfunction and ineffective adenosine triphosphate (ATP) production. This situation severely affected cytoskeletal dynamics. Whereas the control cells had well-defined structures, the AI-exposed astrocytoma cells appeared as globular structures. Creatine kinase (CK) and profilin-2, two critical modulators of cellular morphology, were markedly diminished in the astrocytoma cells treated with AI. Antioxidants such as a-ketoglutarate and N-acetylcysteine mitigated the occurrence of the globular-shaped cells promoted by AI toxicity. Taken together, these data reveal an intricate link between ATP metabolism and astrocytic dysfunction and provide molecular insights into the pathogenesis of AI-induced neurological diseases. (C) 2008 Wiley-Liss, Inc.