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Less than perfect divorces: dysregulated mitochondrial fission and neurodegeneration

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Abstract

Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission. We now know that in mammalian cells mitochondrial fission is mediated by the large GTPase dynamin-related protein 1 (Drp1) acting in concert with outer mitochondrial membrane (OMM) proteins such as Fis1, Mff, and Mief1. It is also generally accepted that organelle fusion depends on the action of three large GTPases: mitofusins (Mfn1, Mfn2) mediating membrane fusion on the OMM level, and Opa1 which is essential for inner mitochondrial membrane fusion. Significantly, mutations in Drp1, Mfn2, and Opa1 have causally been linked to neurodegenerative conditions. Despite this knowledge, crucial questions such as to how fission of the inner and outer mitochondrial membranes are coordinated and how these processes are integrated into basic physiological processes such as apoptosis and autophagy remain to be answered in detail. In this review, we will focus on what is currently known about the mechanism of mitochondrial fission and explore the pathophysiological consequences of dysregulated organelle fission with a special focus on neurodegenerative conditions, including Alzheimer’s, Huntington’s and Parkinson’s disease, as well as ischemic brain damage.

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Correspondence to Stephan Frank.

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B. Oettinghaus and M. Licci contributed equally to this work.

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Oettinghaus, B., Licci, M., Scorrano, L. et al. Less than perfect divorces: dysregulated mitochondrial fission and neurodegeneration. Acta Neuropathol 123, 189–203 (2012). https://doi.org/10.1007/s00401-011-0930-z

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  • DOI: https://doi.org/10.1007/s00401-011-0930-z

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