Dataset Information

Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10.

ABSTRACT: The endoplasmic reticulum-mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level. Here we report that conserved surface areas on opposite sides of the Mdm10 ?-barrel interact with SAM and ERMES, respectively. We generated point mutants to separate protein assembly (SAM) from morphology and phospholipid homeostasis (ERMES). Our study reveals that the ?-barrel channel of Mdm10 serves different functions. Mdm10 promotes the biogenesis of ?-helical and ?-barrel proteins at SAM and functions as integral membrane anchor of ERMES, demonstrating that SAM-mediated protein assembly is distinct from ER-mitochondria contact sites.

SUBMITTER: Ellenrieder L

PROVIDER: S-EPMC5476798 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10.

Ellenrieder Lars L Opaliński Łukasz Ł Becker Lars L Krüger Vivien V Mirus Oliver O Straub Sebastian P SP Ebell Katharina K Flinner Nadine N Stiller Sebastian B SB Guiard Bernard B Meisinger Chris C Wiedemann Nils N Schleiff Enrico E Wagner Richard R Pfanner Nikolaus N Becker Thomas T

Nature communications 20161010

The endoplasmic reticulum-mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level. Here we r ...[more]

PMID: 27721450

Similar Datasets

Project description:Subcellular organelles communicate with each other to regulate function and coordinate responses to changing cellular conditions. The physical-functional coupling of the endoplasmic reticulum (ER) with mitochondria allows for the direct transfer of Ca2+ between organelles and is an important avenue for rapidly increasing mitochondrial metabolic activity. As such, increasing ER-mitochondrial coupling can boost the generation of ATP that is needed to restore homeostasis in the face of cellular stress. The mitochondrial unfolded protein response (mtUPR) is activated by the accumulation of unfolded proteins in mitochondria. Retrograde signaling from mitochondria to the nucleus promotes mtUPR transcriptional responses aimed at restoring protein homeostasis. It is currently unknown whether the changes in mitochondrial-ER coupling also play a role during mtUPR stress. We hypothesized that mitochondrial stress favors an expansion of functional contacts between mitochondria and ER, thereby increasing mitochondrial metabolism as part of a protective response. Hela cells were treated with doxycycline, an antibiotic that inhibits the translation of mitochondrial-encoded proteins to create protein disequilibrium. Treatment with doxycycline decreased the abundance of mitochondrial encoded proteins while increasing expression of CHOP, C/EBPβ, ClpP, and mtHsp60, markers of the mtUPR. There was no change in either mitophagic activity or cell viability. Furthermore, ER UPR was not activated, suggesting focused activation of the mtUPR. Within 2 h of doxycycline treatment, there was a significant increase in physical contacts between mitochondria and ER that was distributed throughout the cell, along with an increase in the kinetics of mitochondrial Ca2+ uptake. This was followed by the rise in the rate of oxygen consumption at 4 h, indicating a boost in mitochondrial metabolic activity. In conclusion, an early phase of the response to doxycycline-induced mitochondrial stress is an increase in mitochondrial-ER coupling that potentiates mitochondrial metabolic activity as a means to support subsequent steps in the mtUPR pathway and sustain cellular adaptation.

Dataset Information

Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10.

Publications

Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets