PXD020281

PXD020281 is an original dataset announced via ProteomeXchange.

Title	MacroD1 sustains mitochondrial integrity and oxidative metabolism
Description	The mono-ADP-ribosylhydrolase MacroD1 has recently been described to exclusively localize to mitochondria. However, to what extent and how MacroD1 controls metabolic homeostasis remains poorly understood. Here, we identify MacroD1 as a mitochondrial regulator of carbohydrate metabolism. Loss of MacroD1 in mice reduced mitochondrial load and compromised muscle function leading to decreased maximal exercise capacity. Mechanistically, knockdown of MacroD1 in C2C12 cells resulted in increased mitochondrial ROS production that ultimately led to increased mitochondrial fission. In line with these findings, proteomic and stable isotope assisted metabolomic profiling revealed that loss of MacroD1 increased glucose uptake and rewired the metabolite flux from glucose to the pentose-phosphate cycle rather than the tricarboxylic acid cycle, which increased the cells dependency on glycolysis. Glucose- and insulin-tolerance tests further showed enhanced peripheral glucose clearance following loss-of MacroD1. Together, our findings identify MacroD1 as novel regulator of metabolic homeostasis by coordinating the cellular carbohydrate fluxes and maintaining mitochondrial function.
HostingRepository	PRIDE
AnnounceDate	2025-05-16
AnnouncementXML	Submission_2025-05-16_05:51:20.767.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Deena Leslie Pedrioli
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	adenosine diphosphoribosyl (ADP-ribosyl) modified residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-09 17:20:48	ID requested
⏵ 1	2025-05-16 05:51:21	announced

Dataset with its publication pending

submitter keyword: Mitochondrial fission,MacroD1, Mitochondrial ADP-ribosylation, ADP-ribosylome, Glucose metabolism, Label-free Quantification

Michael O. Hottiger
contact affiliation	Department of Molecular Mechanisms of Disease University of Zurich Winterthurerstr. 190 8057 Zurich, Switzerland
contact email	michael.hottiger@dmmd.uzh.ch
lab head
Deena Leslie Pedrioli
contact affiliation	University of Zürich
contact email	deena.lesliepedrioli@dmmd.uzh.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020281
     1. Label: PRIDE project
     2. Name: MacroD1 sustains mitochondrial integrity and oxidative metabolism