. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell. 2004 Dec 17;119(6):873-87. PubMed.

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  1. Mitochondria in Alzheimer Disease: Pulling the Plug on the Synapse
    Zheng Li and colleagues provide compelling data and discussion to confirm the growing suspicion that proper mitochondrial structure and function are requisite for synaptic operation. Indeed, it is not only mitochondrial function that is important, but also the location of these organelles. Through the use of transfected dynamin family GTPases (Drp1 and OPA1), which regulate mitochondrial fission and distribution, Morgan Sheng’s group demonstrate that the localization of presynaptic mitochondria are a limiting factor in synapse creation and maintenance. In addition, their data suggest that neuronal activity also contributes to region-specific mitochondrial allocations (Li et al., 2004).

    While the role of mitochondria in the dendritic spine and synapse remain open for definitive explorations, their ATP-manufacturing and calcium-regulating properties may support the necessary microenvironment for spine and synapse activity. However, as the authors remind us, knowledge about mitochondrial movement and co-related synapse activity is sparse at best.

    Synaptic loss and mitochondrial dysfunction are both associated with Alzheimer disease (AD) (Hirai et al., 2001) and connecting the two, as shown by this present work, is attractive. In addition, the neuronal cytoskeleton, responsible for intracellular organelle transport, is also defective in AD pathogenesis (Cash et al., 2003) and likely plays a synergistic role in affecting the intracellular location of mitochondria. As with other paradigms in AD, such defects eventually reach a critical mass and lead to occult pathology and disease (Zhu et al., 2004).

    References:

    . The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell. 2004 Dec 17;119(6):873-87. PubMed.

    . Mitochondrial abnormalities in Alzheimer's disease. J Neurosci. 2001 May 1;21(9):3017-23. PubMed.

    . Is Alzheimer's disease a mitochondrial disorder?. Neuroscientist. 2002 Oct;8(5):489-96. PubMed.

    . Alzheimer's disease: the two-hit hypothesis. Lancet Neurol. 2004 Apr;3(4):219-26. PubMed.

    View all comments by George Perry

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