Dysfunction of mitochondria is frequently proposed to be involved in neurodegenerative disease. Deficiencies in energy supply, free radical generation, Ca(2+) buffering or control of apoptosis, could all theoretically contribute to progressive decline of the central nervous system. Parkinson disease illustrates how mutations in very different genes finally impinge directly or indirectly on mitochondrial function, causing subtle but finally fatal dysfunction of dopaminergic neurons. Neurons in general appear more sensitive than other cells to mutations in genes encoding mitochondrial proteins. Particularly interesting are mutations in genes such as Opa1, Mfn1 and Dnm1l, whose products are involved in the dynamic morphological alterations and subcellular trafficking of mitochondria. These indicate that mitochondrial dynamics are especially important for the long-term maintenance of the nervous system. The emerging evidence clearly demonstrates the crucial role of specific mitochondrial functions in maintaining neuronal circuit integrity.