github link
Accession IconGSE145895

Regulation of endoplasmic reticulum-mitochondria contacts and mitochondrial dynamics by Sel1L-Hrd1 ERAD during thermogenesis

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 2.1 ST Array (mogene21st)

Submitter Supplied Information

Description
Organelles such as endoplasmic reticulum (ER) and mitochondria interact with each other at specialized domains on the ER known as mitochondria-associated membranes (MAMs). Here, using three-dimensional high-resolution imaging techniques, we show that the Sel1LHrd1 protein complex, the most conserved branch of ER-associated protein degradation (ERAD), exerts a profound impact on ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover and hence the abundance of the MAM protein sigma receptor 1 (SigmaR1). Sel1L or Hrd1 deficiency in brown adipocytes impairs dynamic interaction between ER and mitochondria, leading to the formation of pleomorphic “megamitochondria” and, in some cases with penetrating ER tubule(s), in response to acute cold challenge. Mice with ERAD deficiency are cold sensitive and exhibit mitochondrial dysfunction in brown adipocytes. Mechanistically, endogenous SigmaR1 is targeted for proteasomal degradation by Sel1L-Hrd1 ERAD, whose accumulation in ERAD-deficient cells leads to mitofusin 2 (Mfn2) oligomerization, thereby linking ERAD to mitochondrial dynamics. Our study identifies Sel1L-Hrd1 ERAD as a critical determinant of ER-mitochondria contacts, thereby regulating mitochondrial dynamics and thermogenesis.
PubMed ID
Total Samples
12
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Processing Information
Additional Metadata
No rows found
Loading...