Topic
ERMES complex
About: ERMES complex is a research topic. Over the lifetime, 40 publications have been published within this topic receiving 6238 citations.
Papers
TL;DR: It is shown that mitofusin 2, a mitochondrial dynamin-related protein mutated in the inherited motor neuropathy Charcot–Marie–Tooth type IIa, is enriched at the ER–mitochondria interface, and that it tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca2+ uptake.
Abstract: Juxtaposition between endoplasmic reticulum (ER) and mitochondria is a common structural feature, providing the physical basis for intercommunication during Ca(2+) signalling; yet, the molecular mechanisms controlling this interaction are unknown. Here we show that mitofusin 2, a mitochondrial dynamin-related protein mutated in the inherited motor neuropathy Charcot-Marie-Tooth type IIa, is enriched at the ER-mitochondria interface. Ablation or silencing of mitofusin 2 in mouse embryonic fibroblasts and HeLa cells disrupts ER morphology and loosens ER-mitochondria interactions, thereby reducing the efficiency of mitochondrial Ca(2+) uptake in response to stimuli that generate inositol-1,4,5-trisphosphate. An in vitro assay as well as genetic and biochemical evidences support a model in which mitofusin 2 on the ER bridges the two organelles by engaging in homotypic and heterotypic complexes with mitofusin 1 or 2 on the surface of mitochondria. Thus, mitofusin 2 tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake.
2,326 citations
TL;DR: In this article, the authors identified the Mmm1/Mdm10/mdm12/mdr34 complex as a molecular tether between the endoplasmic reticulum (ER) and mitochondria.
Abstract: Communication between organelles is an important feature of all eukaryotic cells. To uncover components involved in mitochondria/endoplasmic reticulum (ER) junctions, we screened for mutants that could be complemented by a synthetic protein designed to artificially tether the two organelles. We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. The tethering complex was composed of proteins resident of both ER and mitochondria. With the use of genome-wide mapping of genetic interactions, we showed that the components of the tethering complex were functionally connected to phospholipid biosynthesis and calcium-signaling genes. In mutant cells, phospholipid biosynthesis was impaired. The tethering complex localized to discrete foci, suggesting that discrete sites of close apposition between ER and mitochondria facilitate interorganelle calcium and phospholipid exchange.
1,273 citations
TL;DR: PDZD8 represents a critical ER-mitochondria tethering protein in metazoans and is suggested to be involved in the regulation of dendritic Ca2+ dynamics in mammalian neurons.
Abstract: Interfaces between organelles are emerging as critical platforms for many biological responses in eukaryotic cells. In yeast, the ERMES complex is an endoplasmic reticulum (ER)–mitochondria tether composed of four proteins, three of which contain a SMP (synaptotagmin-like mitochondrial-lipid binding protein) domain. No functional ortholog for any ERMES protein has been identified in metazoans. Here, we identified PDZD8 as an ER protein present at ER-mitochondria contacts. The SMP domain of PDZD8 is functionally orthologous to the SMP domain found in yeast Mmm1. PDZD8 was necessary for the formation of ER-mitochondria contacts in mammalian cells. In neurons, PDZD8 was required for calcium ion (Ca 2+ ) uptake by mitochondria after synaptically induced Ca 2+ -release from ER and thereby regulated cytoplasmic Ca 2+ dynamics. Thus, PDZD8 represents a critical ER-mitochondria tethering protein in metazoans. We suggest that ER-mitochondria coupling is involved in the regulation of dendritic Ca 2+ dynamics in mammalian neurons.
400 citations
TL;DR: Critically, it is shown that mitochondria are dependent on having one of two contact sites, ERMES or vCLAMP, and the absence of one causes expansion of the other, and elimination of both is lethal.
378 citations
TL;DR: A contact site named vCLAMP is identified that integrates mitochondria with the lysosome-like vacuole and thus the endocytic pathway and Thus, the persistence of vCLAMPs is regulated by phosphorylation of Vps39 and is strongly reduced during respiratory growth.
333 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 3 |
| 2019 | 3 |
| 2018 | 2 |
| 2017 | 3 |
| 2016 | 7 |
| 2015 | 3 |