PXD056917

PXD056917 is an original dataset announced via ProteomeXchange.

Title	BRD4-mediated epigenetic regulation of endoplasmic reticulum-mitochondria contact sites is governed by the mitochondrial complex III
Description	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.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_16:16:21.207.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Orbitrap Astral; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-17 14:31:33	ID requested
⏵ 1	2026-06-07 16:16:22	announced

10.1016/j.molcel.2026.01.012;

submitter keyword: Endoplasmic reticulum-mitochondria contact sites, bromodomain protein, mitochondrial electron transport chain., high-throughput screening

Joseph D. Mancias, MD, PhD
contact affiliation	Harvard Institutes of Medicine 2nd floor, Room 221 4 Blackfan Circle Boston, MA 02115
contact email	Joseph_Mancias@DFCI.HARVARD.EDU
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056917
     1. Label: PRIDE project
     2. Name: BRD4-mediated epigenetic regulation of endoplasmic reticulum-mitochondria contact sites is governed by the mitochondrial complex III