終了Zasshikai seminar 1959th, Dr Ganna PANASYUK, “Nuclear nutrient sensing signaling of Class 3 PI3K in metabolic homeostasis”
Nov.11
- 日時
- 2024/11/11 15:00〜
- 会場
- 2F Lecture room, Chemistry Main Bldg.
- 講師
- Dr. Ganna PANASYUK (Laboratory of Nutrient Sensing Mechanisms, Inserm U1151/CNRS UMR 8253, Institute Necker Enfants Malades (INEM), France)
- 演目
- “Nuclear nutrient sensing signaling of Class 3 PI3K in metabolic homeostasis”
- 担当
- Prof. Takeaki Ozawa (ext.24351), Department of Chemistry, Graduate School of Science
Abstract：In the Panasyuk Lab, we seek to understand How do cells coordinate resilience pathways to adapt to major metabolic challenges like fasting? While acute nutrient deprivation deploys catabolic programs in the cytosol such as lysosomal degradation by autophagy, an adaptation to prolonged fasting relies on transcriptional rewiring. In physiology, the coordination of these major nutrient stress response pathways is essential for survival and the failure of their orchestration accompanies human diseases such as metabolic syndrome or cancer. We focus on still largely enigmatic phosphatidylinositol 3-kinase (PI3K) signaling, a master regulator of autophagy and lysosomal activity, yet its direct role in transcriptional rewiring in fasting is unexplored. Lipid kinase class 3 PI3K generates PI3P, a membrane-born messenger critical at multiple steps for autophagy and vesicular trafficking. In our prior work, we demonstrated that class 3 PI3K lipid kinase triggers selective autophagy of transcriptional repressors to activate mitochondrial biogenesis and lipid catabolism in fasting. In our recent study, we reported that, in addition to its known functions in autophagy, both subunits of class 3 PI3K interact with RNA Pol2, co-localize with active transcription sites and can potently co-activate the circadian clock transcription factor to assure metabolic rhythmicity in liver. In this presentation, I will discuss our the most recent findings that place class 3 PI3K at the nexus of the nuclear transcription by orchestrating the epigenetic rewiring for metabolic adaptation in fasting. I will share our mechanistic insights in the analyses of epigenetic regulators and RNA Pol2-driven transcription downstream of class 3 PI3K. Our findings lay a foundation for further functional investigations of nuclear nutrient sensing signaling of class 3 PI3K in physiology and disease states.
