BRD4-mediated epigenetic regulation of endoplasmic reticulum-mitochondria contact sites is governed by the mitochondrial complex III
Chen, B.; Stark, D. C.; Jadhav, P. V.; Lynn-Nguyen, T. M.; Halligan, B. S.; Rossiter, N. J.; Sindoni, N.; Shin, M.; Paulo, J. A.; Chang, M.; Koo, I.; Koshkin, S.; Eyunni, S.; Ronchi, P.; Paulsen, M. T.; Morlacchi, P.; Hanna, D. A.; Lin, J.; Guerra, R. M.; Pagliarini, D.; Banerjee, R.; Parolia, A.; Ljungman, M.; Patterson, A. D.; Mancias, J. D.; Mosalaganti, S.; Sexton, J.; Cali, T.; Lyssiotis, C. A.; Shah, Y. M.
Show abstract
Inter-organellar communication is critical for cellular metabolic homeostasis. One of the most abundant inter-organellar interactions are those at the endoplasmic reticulum and mitochondria contact sites (ERMCS). However, a detailed understanding of the mechanisms governing ERMCS regulation and their roles in cellular metabolism are limited by a lack of tools that permit temporal induction and reversal. Through unbiased screening approaches, we identified fedratinib, an FDA-approved drug, that dramatically increases ERMCS abundance by inhibiting the epigenetic modifier BRD4. Fedratinib rapidly and reversibly modulates mitochondrial and ER morphology and alters metabolic homeostasis. Moreover, ERMCS modulation depends on mitochondria electron transport chain complex III function. Comparison of fedratinib activity to other reported inducers of ERMCS revealed common mechanisms of induction and function, providing clarity and union to a growing body of experimental observations. In total, our results uncovered a novel epigenetic signaling pathway and an endogenous metabolic regulator that connects ERMCS and cellular metabolism.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Hexokinase detachment from mitochondria drives the Warburg effect to support compartmentalized ATP production 97%
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology 96%
- Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression 96%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- LRRK2 and Rab10 Coordinate Macropinocytosis to Mediate Immunological Responses in Phagocytes 96%
- PERK Signaling Promotes Mitochondrial Elongation By Remodeling Membrane Phosphatidic Acid 95%
- The Proxitome of Arabidopsis Processing Bodies Reveals a Condensate-Membrane Interface Instructing Actin-Driven Directional Growth 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.