C-terminal binding protein maintains mitochondrial activities.
Mitochondria are essential organelles that are responsible for cellular energy production and cell death in response to various stimuli. Although C-terminal binding protein (CtBP) functions as a metabolic sensor in transcriptional corepressor complex, it is unclear whether CtBP controls gene transcription in response to metabolic stress. In this study, we found that CtBP represses Bcl-2-associated X protein (Bax) transcription in glucose-rich media by binding to the E-box region of the Bax promoter. Glucose withdrawal leads to the dissociation of CtBP from the Bax promoter and significant changes of the histone codes in the Bax promoter. CtBP knockout increases Bax transcription, ablates mitochondrial morphology and reduces mitochondrial activities. Ectopic expression of CtBP or knockdown of Bax in ctbp-knockout cells recovers mitochondrial morphology and function, suggesting that CtBP functions as a metabolic sensor that maintains mitochondrial activities. Our findings provide insights into how the intracellular energy level is reflected into gene transcription involved in mitochondrial morphology and function.
Kim
J H
JH
National Research Laboratory for Metabolic Checkpoint, Department of Biomedical Sciences & Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Youn
H D
HD
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D051028:bcl-2-Associated X Protein / Q000235:genetics
D004268:DNA-Binding Proteins; D051028:bcl-2-Associated X Protein; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D005947:Glucose