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Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes.

ABSTRACT: 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.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC7409365 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The endoplasmic reticulum (ER)-associated degradation system regulates aggregation and degradation of mutant neuroserpin.

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