BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis.

ABSTRACT: The breast cancer susceptibility gene 1 (BRCA1) is a major tumor suppressor gene and is most frequently mutated in hereditary breast cancer. BRCA1 plays a critical role in many biological processes, especially maintaining genomic stability in the nucleus, yet its role in the cytoplasm remains elusive. Here, it is revealed that BRCA1 maintains a healthy mitochondrial network through regulating mitochondrial dynamics, including fission and fusion. BRCA1 deficiency causes dysfunctional mitochondrial dynamics through increased expression of mitofusin1/2. With mitochondrial stress, BRCA1 is recruited to the mitochondrial outer membrane, where it plays an essential role in maintaining a healthy mitochondrial network. Consequently, BRCA1 deficiency impairs stress-induced mitophagy through

SUBMITTER: Chen Q 

PROVIDER: S-EPMC7080549 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature