PXD072078-1

PXD072078 is an original dataset announced via ProteomeXchange.

Title	β-Nicotinamide mononucleotide restores mitochondrial function and muscle strength in septic male mice
Description	Sepsis remains a leading cause of mortality and long-term disability, with survivors frequently developing intensive care unit–acquired weakness (ICU-AW) as part of post-intensive care syndrome. To identify a nutritional therapy for ICU-AW, we investigated the mechanisms underlying sepsis- induced skeletal muscle dysfunction using a cecal slurry-induced sepsis mouse model. Although body weight and skeletal muscle mass recovered 14 days after sepsis induction, muscle strength remained impaired, accompanied by persistent mitochondrial abnormalities. Transcriptomic analysis revealed that the pathways termed the ‘sirtuin signaling pathway’ and ‘mitochondrial dysfunction’ significantly enriched with downregulation of Sirt3 which is a major mitochondrial nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase. Biochemical analyses confirmed increased acetylated lysine of mitochondrial proteins in septic muscle tissue. Among these proteins, mass spectrometry identified complex I subunits as candidate substrates of Sirt3. Knockdown of Sirt3 in C2C12 myotubes impaired mitochondrial respiration, whereas treatment with β-nicotinamide mononucleotide (β-NMN) partially rescued energy production. In vivo, acute-phase administration of β-NMN preserved mitochondrial morphology and restored muscle strength without altering muscle mass. These findings demonstrate that sepsis induces mitochondrial dysfunction and persistent muscle weakness through Sirt3 downregulation, and highlights β-NMN supplementation as a promising NAD⁺-targeted therapeutic strategy for mitigating ICU-AW.
HostingRepository	PRIDE
AnnounceDate	2026-03-01
AnnouncementXML	Submission_2026-02-28_20:38:18.939.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Atsushi Yokoyama
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-16 22:40:32	ID requested
⏵ 1	2026-02-28 20:38:19	announced
2	2026-03-16 04:09:57	announced	2026-03-16: Updated project metadata.

Dataset with its publication pending

submitter keyword: skeletal muscle weakness, sepsis, mitochondria ICU-acquired weakness (ICU-AW),β-NMN

Yuuki Imai
contact affiliation	Division of Integrative Pathophysiology, Proteo-Science Center, PIAS, Ehime University, Japan
contact email	y-imai@m.ehime-u.ac.jp
lab head
Atsushi Yokoyama
contact affiliation	Tohoku University
contact email	atsushi.yokoyama.c6@tohoku.ac.jp
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072078
     1. Label: PRIDE project
     2. Name: β-Nicotinamide mononucleotide restores mitochondrial function and muscle strength in septic male mice