The “sweet” side of ER-mitochondria contact sites

Abstract

The regions at which the ER and mitochondria come into close proximity, known as ER-mitochondria contact sites provide essential platforms for the exchange of molecules between the two organelles and the coordination of various fundamental cellular processes. In addition to the well-established role of ER-mitochondria interfaces in calcium and lipid crosstalk, emerging evidence supports that a proper communication between ER and mitochondria is critical for the regulation of mitochondrial morphology and the initiation of autophagy. Within this context, our recent data indicate that glycogen is targeted to ER-mitochondria contacts through the Stbd1 protein, a proposed autophagy receptor for glycogen. Glycogen-bound Stbd1 influences ER-mitochondria tethering and the morphology of the mitochondrial network. We here suggest possible roles of glycogen recruitment to ER-mitochondria contact sites. Stbd1-mediated targeting of glycogen to ER-mitochondria junctions could represent a mechanism through which glycogen is sequestered into autophagosomes for lysosomal degradation, a process described as glycogen autophagy or glycophagy. Additionally, we discuss a possible mechanism which links the observed effects of Stbd1 on mitochondrial morphology with the previously reported impact of nutrient availability on mitochondrial dynamics. In this model we propose that glycogen-bound Stbd1 signals nutrient status to ER-mitochondria junctions resulting in adaptations in the morphology of the mitochondrial network.

Keywords

• endoplasmic reticulum
• ER-mitochondria contact sites
• glycogen
• glycophagy
• mitochondria
• mitochondria-associated membranes
• N-myristoylation
• Stbd1