Despite intense research efforts investigating the pathophysiology of Alzheimer's disease (AD), it is still unclear how amyloid β accumulation leads to neuronal dysfunction, although mitochondrial failure has been suggested as a causative agent. Mitochondrial function is intimately linked to its ability to communicate with other organelles. In the case of the ER, mitochondria exchange outer membrane lipids or proteins with the ER through mitochondria–ER contacts (MERCs). In their paper, Laura Morelli and colleagues (Martino Adami et al., 2019) analyse MERCs in rat hippocampal neurons that express a mutant of human amyloid precursor protein. They find that at 14 days in vitro (DIV), but not 7 DIV, neurons with the transgene show fragmented mitochondrial cristae and ER swelling. To inspect the differences in MERCs between wild-type and transgenic neurons before onset of AD pathology, the authors therefore investigate MERCs after 7 DIV. Using a fluorescence resonance energy transfer assay and transmission electron microscopy, they demonstrate that tight MERCs of less than 10 nm are less prevalent in transgenic neurons. Moreover, these cells display an altered mitochondrial lipid and bioenergetics profile. Taken together, these results suggest that MERCs are restructured in the presence of mutant amyloid precursor protein, which might contribute to the neuronal dysfunction observed in AD.
A potential role for mitochondria–ER contacts in the pathology of Alzheimer's disease
A potential role for mitochondria–ER contacts in the pathology of Alzheimer's disease. J Cell Sci 15 October 2019; 132 (20): e2002. doi:
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