Related Experiment Videos

ZNF143 suppresses mitophagy to drive MASLD progression by regulating SMURF1/TRPV1 axis

Mei Long1, Kewei Tan2, Yujie Dong3

  • 1Department of Rheumatology and Immunology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Molecular Genetics and Genomics : MGG
|August 10, 2026
PubMed

Insights

Zinc finger protein 143 (ZNF143) worsens metabolically dysfunction-associated steatotic liver disease (MASLD) by hindering mitophagy. Reducing ZNF143 improves liver health by restoring mitophagy through the SMURF1-TRPV1 pathway.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cell Biology

Background:

  • Metabolically dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder.
  • Impaired mitophagy is increasingly recognized in MASLD pathogenesis.
  • The precise regulatory mechanisms of mitophagy in MASLD remain unclear.

Purpose of the Study:

  • To investigate the role of Zinc finger protein 143 (ZNF143) in regulating hepatocyte mitophagy during MASLD.
  • To elucidate the underlying molecular mechanisms by which ZNF143 influences MASLD progression.

Main Methods:

  • Utilized high-fat diet (HFD)-induced MASLD mouse models and free fatty acid (FFA)-treated Huh-7 cells.
  • Assessed pathological changes, lipid deposition, and mitochondrial damage via H&E, Oil Red O, JC-1 staining, and TEM.
  • Investigated molecular interactions using dual-luciferase reporter assay, ChIP, and Co-IP.

Main Results:

  • ZNF143 expression was upregulated in MASLD models.
  • ZNF143 knockdown ameliorated lipid accumulation and liver injury by enhancing hepatocyte mitophagy.
  • ZNF143 transcriptionally activated SMURF1, leading to TRPV1 ubiquitination and degradation.

Conclusions:

  • ZNF143 exacerbates MASLD progression by promoting TRPV1 ubiquitination and degradation via SMURF1 activation.
  • Targeting ZNF143 may offer a therapeutic strategy for MASLD by restoring mitophagy.
Keywords:
Metabolically dysfunction-associated steatotic liver diseaseMitophagySMURF1TRPV1ZNF143

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...