p62 is involved in the mechanism of Mallory body formation

Li Nan1, Yong Wu, Fawzia Bardag-Gorce

  • 1Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

Insights

p62 protein is crucial for Mallory body formation in liver cells. Inhibiting p62 significantly reduced Mallory body development, while overexpressing it accelerated their formation.

Area of Science:

  • Hepatology
  • Cell Biology
  • Protein Degradation

Background:

  • p62 is a scaffolding protein that binds polyubiquitin and participates in proteasomal degradation.
  • Mallory bodies (MBs) are protein aggregates found in hepatocytes, implicated in liver injury.

Purpose of the Study:

  • To investigate the role of p62 in the formation of Mallory bodies (MBs).

Main Methods:

  • Primary mouse hepatocytes were cultured and treated with drug-priming.
  • p62 expression was inhibited using gene-specific gripNA (gp62).
  • p62 overexpression was achieved via transfection with p62-green fluorescent protein (GFP) plasmid.

Main Results:

  • gp62 treatment inhibited MB formation by 94% in drug-primed hepatocytes, decreasing levels of p62, ubiquitin (Ub), and cytokeratin 8 (CK8).
  • Overexpression of p62 enhanced MB formation by 339% in drug-primed hepatocytes.
  • p62 overexpression in normal hepatocytes induced Ub-positive, CK8-negative MB-like aggresomes.

Conclusions:

  • p62 plays a critical role in the mechanism of Mallory body formation.
  • Modulating p62 levels affects the development of hepatic protein aggregates.

Related Concept Videos

Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
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...
Transport Across the Golgi01:26

Transport Across the Golgi

While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...