ER-Mitochondria signaling regulates autophagy.

ER-Mitochondria signaling regulates autophagy.
Autophagy. 2017 May 26;:0
Authors: Gomez-Suaga P, Paillusson S, Miller CCJ
Abstract
The endoplasmic reticulum (ER) and mitochondria form tight functional contacts that regulate a number of key cellular processes. The formation of these contacts involves "tethering proteins" that function to recruit regions of ER to mitochondria. The integral ER protein VAPB (VAMP associated protein B and C) binds to the outer mitochondrial membrane protein, RMDN3/PTPIP51 (regulator of microtubule dynamics 3) to form one such set of tethers. Recently, we showed that the VAPB-RMDN3 tethers regulate macroautophagy/autophagy. Small interfering RNA (siRNA) knockdown of VAPB or RMDN3 to loosen ER-mitochondria contacts stimulates autophagosome formation, whereas overexpression of VAPB or RMDN3 to tighten contacts inhibit their formation. Artificial tethering of ER and mitochondria via expression of a synthetic linker protein also reduces autophagy and this artificial tether rescues the effects of VAPB- or RMDN3-targeted siRNA loss on autophagosome formation. Finally, our studies revealed that the modulatory effects of ER-mitochondria contacts on autophagy involve their role in mediating ITPR (inositol 1,4,5-trisphosphate receptor) delivery of Ca(2+) from ER stores to mitochondria.
PMID: 28548902 [PubMed - as supplied by publisher]

Source: Autophagy - May 26, 2017 Category: Cytology Authors: Gomez-Suaga P, Paillusson S, Miller CCJ Tags: Autophagy Source Type: research