. ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat Commun. 2014 Jun 3;5:3996. PubMed.

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  1. The finding of a VAPB-PTPIP51 interaction supporting the ER-mitochondria association is interesting and convincing. The effects of TDP-43 overexpression suggest a potential role for TDP-43 in modulating this ER-mitochondrial association and intracellular calcium signaling. However, from results in the paper, the effects of TDP43 appear to be indirect and mediated via GSK-3β. It will be important to determine if impaired ER-mitochondrial association is a major outcome of TDP-43/GSK-3β activation or if it is one of many downstream pathways leading to pathology in TDP-43 ALS. Nevertheless, the potential link between TDP-43 and intracellular calcium signaling is very interesting.

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