作者
Phillip A Dumesic, Daniel F Egan, Philipp Gut, Mei T Tran, Alice Parisi, Nirmalya Chatterjee, Mark Jedrychowski, Margherita Paschini, Lawrence Kazak, Sarah E Wilensky, Florence Dou, Dina Bogoslavski, Jeffrey A Cartier, Norbert Perrimon, Shingo Kajimura, Samir M Parikh, Bruce M Spiegelman
发表日期
2019/7/2
期刊
Cell metabolism
卷号
30
期号
1
页码范围
190-200. e6
出版商
Elsevier
简介
Mitochondrial abundance and function are tightly controlled during metabolic adaptation but dysregulated in pathological states such as diabetes, neurodegeneration, cancer, and kidney disease. We show here that translation of PGC1α, a key governor of mitochondrial biogenesis and oxidative metabolism, is negatively regulated by an upstream open reading frame (uORF) in the 5′ untranslated region of its gene (PPARGC1A). We find that uORF-mediated translational repression is a feature of PPARGC1A orthologs from human to fly. Strikingly, whereas multiple inhibitory uORFs are broadly present in fish PPARGC1A orthologs, they are completely absent in the Atlantic bluefin tuna, an animal with exceptionally high mitochondrial content. In mice, an engineered mutation disrupting the PPARGC1A uORF increases PGC1α protein levels and oxidative metabolism and confers protection from acute kidney injury …
引用总数
201920202021202220232024271111125