The endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known
as mitochondria-associated membranes (MAMs). Here, we used three-dimensional highresolution
imaging to investigate the formation of pleomorphic “megamitochondria” with
altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ERassociated
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 crosstalk and expands our understanding of the
physiological importance of Sel1L-Hrd1 ERAD.
as mitochondria-associated membranes (MAMs). Here, we used three-dimensional highresolution
imaging to investigate the formation of pleomorphic “megamitochondria” with
altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ERassociated
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 crosstalk and expands our understanding of the
physiological importance of Sel1L-Hrd1 ERAD.