Cell biology

Biology

Mesenchymal stem cell

Adipogenesis

Biochemistry

Endoplasmic reticulum

Organelle

Unfolded protein response

Endoplasmic-reticulum-associated protein degradation

Thermogenesis

Mitochondrion

Chemistry

Adipose tissue

Protein degradation

Science

The endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known as mitochondria-associated membranes (MAMs). Here, we used three-dimensional high-resolution imaging to investigate the formation of pleomorphic "megamitochondria" with altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ER-associated protein degradation (ERAD). Mice with ERAD deficiency in brown adipocytes were cold sensitive and exhibited mitochondrial dysfunction. ERAD deficiency affected ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover of the MAM protein, sigma receptor 1 (SigmaR1). Thus, our study provides molecular insights into ER-mitochondrial cross-talk and expands our understanding of the physiological importance of Sel1L-Hrd1 ERAD.

Endoplasmic reticulum–associated degradation regulates mitochondrial dynamics in brown adipocytes