From Mallory to Mallory-Denk bodies: what, how and why?

K Zatloukal, SW French, C Stumptner, P Strnad, M Harada, Diana Toivola, M Cadrin, MB Omary

Research output: Contribution to journalReview Article or Literature Reviewpeer-review

224 Citations (Scopus)

Abstract

Published by Elsevier Inc. Frank B. Mallory described cytoplasmic hyaline inclusions in hepatocytes of patients with alcoholic hepatitis in 1911. These inclusions became known as Mallory bodies (MBs) and have since been associated with a variety of other liver diseases including non-alcoholic fatty liver disease. Helmut Denk and colleagues described the first animal model of MBs in 1975 that involves feeding mice griseofulvin. Since then, mouse models have been instrumental in helping understand the pathogenesis of MBs. Given the tremendous contributions made by Denk to the field, we propose renaming MBs as Mallory-Denk bodies (MDBs). The major constituents of MDBs include keratins 8 and 18 (K8/18), ubiquitin, and p62. The relevant proteins and cellular processes that contribute to MDB formation and accumulation include the type of chronic stress, the extent of stress-induced protein misfolding and consequent proteasome overload, a K8-greater-than-K18 ratio, transamidation of K8 and other proteins, presence of p62 and autophagy. Although it remains unclear whether MDBs serve a bystander, protective or injury promoting function, they do serve an important role as histclogical and potential progression markers in several liver diseases.
Original languageUndefined/Unknown
Pages (from-to)2033–2049
Number of pages17
JournalExperimental Cell Research
Volume313
Issue number10
DOIs
Publication statusPublished - 2007
MoE publication typeA2 Review article in a scientific journal

Keywords

  • chaperones
  • hepatocellular carcinoma
  • idiopathic copper toxicosis
  • inclusion bodies
  • liver disease
  • liver injury
  • NAFLD
  • NASH
  • p62
  • primary biliary cirrhosis
  • Wilson disease
  • ubiquitin
  • intermediate filaments
  • keratins

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