PXD066204

PXD066204 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial ROS-dependent localization and trafficking of glycolytic enzymes to mitochondria
Description	Mitochondrial reactive oxygen species (mtROS) regulate cellular signaling pathways, but also cause oxidative stress when de-regulated during aging and pathological conditions such as neurodegenerative diseases. The dynamic trafficking of proteins between cellular compartments is a common mechanism to control their stability and biological activities. By targeting the BirA* biotin ligase to the outer mitochondrial membrane in HEK293 cells, we identified proteins whose labelling increased or decreased in response to menadione consistent with a change in their trafficking to and from mitochondria in response to increased ROS production. These proteins represent potential candidates for future studies of mitochondrial stress signaling. A subset of glycolytic enzymes was found in this screen and confirmed, by mitochondrial fractionation and imaging, to increase localization to mitochondria in response to menadione, despite no change in their overall abundance. Submitochondrial fractionation studies are consistent with localization of a pool of these enzymes to the mitochondrial intermembrane space. Localization of glycolytic enzymes to mitochondria was also increased in cells grown under hypoxia or that express a mitochondria-targeted D-amino acid oxidase (conditions that induce increased mtROS production), and inhibited basally under normal growth conditions by the mitochondrial antioxidant MnTBAP. Finally, primary Alzheimer’s disease (AD) fibroblasts also had glycolytic enzymes associated with mitochondria that was reversed by antioxidants, consistent with increased mtROS in these cells altering their relative cellular distribution. We speculate that the increased mitochondrial localization of glycolytic enzymes is an adaptive response to mtROS that alters glucose flux toward the antioxidant pentose phosphate pathway, creates distinct regulatory pools of mitochondrial metabolites or new metabolic circuits, and/or provides cytoprotection or other adaptive responses via moonlighting functions unrelated to their enzymatic activity.
HostingRepository	PRIDE
AnnounceDate	2025-08-12
AnnouncementXML	Submission_2025-08-12_06:05:28.495.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Münch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 04:13:53	ID requested
⏵ 1	2025-08-12 06:05:28	announced

10.1016/J.REDOX.2025.103812;

submitter keyword: Mitochondria, MTS-DAO, redox signaling, glycolytic enzymes, oxidative stress, DAO

Christian Münch
contact affiliation	Institute of Molecular Systems Medicine, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany. The Center for Functional Proteomics, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany. Frankfurt Cancer Institute, Frankfurt am Main, Germany. Cardio-Pulmonary Institute, Frankfurt am Main, Germany.
contact email	bozkurt@med.uni-frankfurt.de
lab head
Christian Münch
contact affiliation	Goethe University Frankfurt
contact email	ch.muench@em.uni-frankfurt.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD066204

PRIDE project URI

• PRIDE
  1. PXD066204
     1. Label: PRIDE project
     2. Name: Mitochondrial ROS-dependent localization and trafficking of glycolytic enzymes to mitochondria