PXD066863-1

PXD066863 is an original dataset announced via ProteomeXchange.

Title	Diurnal regulation of Acyl-CoA synthetase 3 (ACSF3) governs rhythmic mitochondrial lysine-malonylation and daily hepatic metabolism
Description	Hepatic daily rhythms are coordinated by feeding and the molecular circadian clock, ensuring metabolic homeostasis. Disrupted feeding schedules promote circadian misalignment and metabolic disease but the underlying mechanisms remain unknown. Post-translational modifications have emerged as key regulators of circadian metabolic outputs. In this framework, mitochondria constitute a central hub, integrating metabolic rhythms, feeding cycles and the circadian clock. Here, we show that the mitochondrial enzyme Acyl-CoA-synthetase-family-member-3 (ACSF3) oscillates in phase with different feeding schedules to drive rhythmic lysine-malonylation and coordinate daily hepatic metabolism. Hepatic ACSF3 knockdown affected lysine-malonylation rhythms, decreased fasting glycemia, insulin sensitivity and AKT phosphorylation. It also shifted lipid oxidation from mitochondria to peroxisomes, enhanced de novo lipogenesis and triglyceride synthesis, while increasing diurnal autophagy. Integrated multi-omics profiling uncovered specific lysine-malonylation targets in glycolysis, the TCA cycle, fatty-acid oxidation and autophagy. Our findings establish ACSF3 as a critical link between feeding time, protein malonylation, and diurnal liver metabolism.
HostingRepository	PRIDE
AnnounceDate	2026-07-07
AnnouncementXML	Submission_2026-07-07_00:38:55.637.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yohann Couté
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	N6-malonyl-L-lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-01 06:33:21	ID requested
⏵ 1	2026-07-07 00:38:56	announced

Dataset with its publication pending

submitter keyword: Quantitative proteomics, ACSF3,Mouse, Circadian Rhythms, Acyl-CoA synthetase 3, SILAC, Liver, Lysine-Malonylation

Yohann Couté
contact affiliation	EDyP
contact email	yohann.coute@cea.fr
lab head
Yohann Couté
contact affiliation	EDyP
contact email	yohann.coute@cea.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066863
     1. Label: PRIDE project
     2. Name: Diurnal regulation of Acyl-CoA synthetase 3 (ACSF3) governs rhythmic mitochondrial lysine-malonylation and daily hepatic metabolism