Related Experiment Video

Updated: Apr 15, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
07:20

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

1.4K

PTPRO-mediated autophagy prevents hepatosteatosis and tumorigenesis

Wenjie Zhang1, Jiajie Hou1, Xiaochen Wang1

  • 1Liver Transplantation Center of The First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.

Oncotarget
|April 1, 2015
PubMed

Insights

Protein tyrosine phosphatase receptor type O (PTPRO) deficiency worsens nonalcoholic steatohepatitis (NASH) by impairing autophagy and lipid metabolism, promoting liver injury and cancer via the PI3K/Akt/p53 pathway.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Metabolic Diseases

Background:

  • Autophagy is crucial in nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC).
  • Protein tyrosine phosphatase receptor type O (PTPRO) is a known tumor suppressor, but its role in NASH is unclear.
  • Investigating PTPRO's role in NASH pathogenesis is essential.

Purpose of the Study:

  • To elucidate the role of PTPRO-dependent autophagy in insulin resistance, lipid metabolism, and hepatocarcinogenesis.
  • To understand the molecular mechanisms linking PTPRO, autophagy, and NASH progression.

Main Methods:

  • Utilized wild-type and ptpro-/- mice fed a high-fat diet (HFD) post-diethylnitrosamine (DEN) injection to model NASH.
  • Analyzed liver injury, insulin resistance, hepatosteatosis, autophagy markers, gene expression (lipogenesis, β-oxidation), and protein levels (AKT, p53, MDMX/MDM2).
  • Examined PTPRO expression and p62 accumulation in human steatohepatitis samples.

Main Results:

  • Ptpro-/- mice showed severe liver injury, insulin resistance, hepatosteatosis, and autophagy deficiency compared to WT mice.
  • PTPRO deletion promoted lipogenic genes, reduced β-oxidation genes, and increased AKT activation and cytoplasmic p53 accumulation, repressing autophagy.
  • Hyperinsulinemia was exacerbated in HFD-fed ptpro-/- mice; AKT activation stabilized MDMX/MDM2, promoting p53 accumulation, while AKT inhibition restored autophagy.

Conclusions:

  • PTPRO regulates insulin and lipid metabolism via the PI3K/Akt/MDM4/MDM2/P53 axis, impacting autophagy.
  • PTPRO deficiency exacerbates HFD-induced steatohepatitis due to hyperinsulinemia and autophagy deficiency.
  • Decreased PTPRO expression in human NASH correlates with increased p62, highlighting PTPRO's critical role in liver health.
Keywords:
AKTPTPROautophagynonalcoholic steatohepatitisp53

More Related Videos

Monitoring Stub1-Mediated Pexophagy08:26

Monitoring Stub1-Mediated Pexophagy

Published on: May 12, 2023

2.2K
Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

1.6K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
6.2K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
10.6K
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...
5.5K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
5.1K