SQSTM1/p62 Controls mtDNA Expression and Participates in Mitochondrial Energetic Adaption via MRPL12.

ABSTRACT: Mitochondrial DNA (mtDNA) encodes thirteen core components of OXPHOS complexes, and its steady expression is crucial for cellular energy homeostasis. However, the regulation of mtDNA expression machinery, along with its sensing mechanism to energetic stresses, is not fully understood. Here, we identified SQSTM1/p62 as an important regulator of mtDNA expression machinery, which could effectively induce mtDNA expression and the effects were mediated by p38-dependent upregulation of mitochondrial ribosomal protein L12 (MRPL12) in renal tubular epithelial cells (TECs), a highly energy-demanding cell type related to OXPHOS. We further identified a direct binding site within the MRPL12 promoter to ATF2, the downstream effector of p38. Besides, SQSTM1/p62-induced mtDNA expression is involved in b

SUBMITTER: Ma Y 

PROVIDER: S-EPMC7452302 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature