Current evidence also shows that the suppression of mitochondrial fission alleviates brain injuries after experimental SAH. In addition, mitochondrial fusion and fission are vital to maintaining cellular functions. Thus, our previous studies strongly suggest that post-SAH hyperglycemia is not only a response to primary insult, but also an aggravating factor for brain injuries. Morphologically, we found that hyperglycemia exacerbated late vasospasm following SAH. Our previous studies have demonstrated that hyperglycemia induces profound neuronal apoptosis of the cerebral cortex. Neurological deficits following subarachnoid hemorrhage (SAH) are caused by early or delayed brain injuries. 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. 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. Significantly, mutations in Drp1, Mfn2, and Opa1 have causally been linked to neurodegenerative conditions.
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.
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. Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission.
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