Intracellular proteolytic systems in alcohol-induced tissue injury

Alcohol Research & Health, Winter, 2003 by Terrence M. Donohue, Jr., Natalia A. Osna

Summary of Cellular Proteolytic Systems*

System         Location      Major Specificity/Function   Alcohol
                                                          Effects

Lysosome**     Cytoplasm     Degrades intracellular       Impairs
                             proteins and proteins taken  activity,
                             up by cellular endocytosis   formation, and
                                                          structural
                                                          integrity of
                                                          lysosomes
Ubiquitin--    Cytoplasm,    Degrades most intracellular  Inhibits
proteasome**   nucleus       proteins as well as damaged  proteasome
                             proteins                     activity;
                                                          leads to
                                                          accumulation
                                                          of ubiquitin--
                                                          protein
                                                          conjugates
Calpains**     Cytoplasm     Degrade cytoskeletal         Activates
                             proteins                     calpains and
                                                          leads to
                                                          aberrant
                                                          hydrolysis of
                                                          cellular
                                                          proteins
Mitochondrial  Mitochondria  Remove oxidatively modified  No known
proteinases                  mitochondrial proteins;      effect
                             partially degrade imported
                             mitochondrial proteins
Membrane       Endoplasmic   Partially degrade            No known
proteinases    reticulum,    secretory, endocytosed, and  effect
               plasma        imported proteins; degrade
               membrane,     newly synthesized faulty
               mitochondria  proteins

* For definitions of terms used in this table, see the Glossary on page
331.
** Indicates that the system is described in greater detail in this
article.

(1) During endocytosis, material outside the cell is progressively enclosed by a portion of the plasma membrane, which then is taken up into the cell to form a bubble-like structure called an endosome, containing the ingested material. Endosomes then fuse with lysosomes so that the lysosomal enzymes gain access to the ingested material.

(2) In immune cells, the proteasome possesses three unique subunits that replace some of the normal subunits. These three unique subunits alter the proteasome, allowing it to degrade target proteins into antigenic peptides that stimulate an immune response.

(3) The process of Mallory body formation is analogous to what occurs in Alzheimer's disease, where ubiquitylated tangles of nerve cell fibers and structures called neuronal bodies form in the brain. The formation of neuronal bodies also is related to reduced proteasome function.