Disruption of the VAPB-PTPIP51 ER-mitochondria tethering proteins in post-mortem human amyotrophic lateral sclerosis

• DOI: 10.3389/fcell.2022.950767
• Publication Date: 2022-08-16T06:49:30Z
• Authors: Naomi Hartopp; Dawn H W. Lau; Sandra M. Martin-...; Andrea Markovinovic; Gábor M. Mórotz; Jenny Greig; Elizabeth B. Glennon; Claire Troakes; Patricia Gomez-Suaga; Wendy Noble; Christopher C.J. ...
• Keywords: Tethering

Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many neuronal functions that are perturbed in amyotrophic lateral sclerosis (ALS) perturbation to ER-mitochondria signaling is seen cell transgenic models of ALS. However, there currently little evidence altered human mediated by interactions integral ER protein VAPB outer mitochondrial membrane PTPIP51 which act recruit “tether” regions surface. The VAPB-PTPI51 tethers now known regulate a number functions. These include delivery Ca 2+ from stores mitochondria, ATP production, autophagy synaptic activity. Here we investigate VAPB-PTPIP51 post-mortem control ALS spinal cords. We show levels reduced Proximity ligation assays were then used quantify interaction cord motor neurons cases. studies revealed disrupted Thus, identify new pathogenic event