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

• DOI: 10.1016/j.isci.2020.101428
• Publication Date: 2020-08-01T16:18:40Z
• Authors: Yuan Ma; Suwei Zhu; Tingting Lv; Xia Gu; Hong Feng; Junhui Zhen; Wei Xin; Qiang Wan
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Functional Aspects of Cell Biology; Science; Q; Cell Biology; Biological Sciences; 16. Peace & justice; Molecular Biology; Article

Mitochondrial DNA (mtDNA) encodes thirteen core components of OXPHOS complexes, and its steady expression is crucial for cellular energy homeostasis. However, the regulation mtDNA machinery, along with sensing mechanism to energetic stresses, not fully understood. Here, we identified SQSTM1/p62 as an important regulator which could effectively induce effects were mediated by p38-dependent upregulation mitochondrial ribosomal protein L12 (MRPL12) in renal tubular epithelial cells (TECs), a highly energy-demanding cell type related OXPHOS. We further direct binding site within MRPL12 promoter ATF2, downstream effector p38. Besides, SQSTM1/p62-induced involved both serum deprivation hypoxia-induced response, was highlighted kidney injury phenotype TECs-specific knockout mice. Collectively, these data suggest that key sensor machinery.