PXD073193

PXD073193 is an original dataset announced via ProteomeXchange.

Title	A Novel Mitochondrial Microprotein Reprograms Cellular Bioenergetics and Protects Against Hepatic Steatosis
Description	Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge with limited therapeutic options. To identify new regulators of lipid metabolism, we developed a novel proteomic strategy combining organelle enrichment with a custom sORF database to explore the “dark proteome.” Using this approach, we discovered MNP33, a previously uncharacterized 28-amino acid microprotein. This novel protein protects against metabolic disease in mice by potently reducing body weight gain, improving glucose homeostasis, and decreasing hepatic triacylglycerol (TAG) accumulation. Mechanistically, MNP33 localizes to the inner mitochondrial membrane, interacts with adenine nucleotide translocase 2 (ANT2), and induces a bioenergetic remodeling characterized by increased proton leak, elevated basal respiration, and a paradoxically elevated membrane potential. This promotion of energy dissipation provides a direct basis for the observed reduction in TAG. Our findings establish MNP33 as a key regulator of hepatic lipid metabolism with therapeutic potential for treating MASLD.
HostingRepository	PRIDE
AnnounceDate	2026-08-13
AnnouncementXML	Submission_2026-08-13_05:17:22.645.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuyan Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-17 09:52:03	ID requested
⏵ 1	2026-08-13 05:17:23	announced

Dataset with its publication pending

submitter keyword: MNP33

microprotein

mitochondrial energetics

energy dissipation

lipid metabolism

hepatic steatosis

MASLD

ANT2

Shuyan Zhang
contact affiliation	Beijing Ditan Hospital, Capital Medical University
contact email	syzhang@ibp.ac.cn
lab head
Shuyan Zhang
contact affiliation	Beijing Ditan Hospital, Capital Medical University
contact email	syzhang@ibp.ac.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073193
     1. Label: PRIDE project
     2. Name: A Novel Mitochondrial Microprotein Reprograms Cellular Bioenergetics and Protects Against Hepatic Steatosis