Inclusion bodies and autophagosomes: Are ER-derived protective organelles different than classical autophagosomes?

A hallmark of some endoplasmic reticulum (ER)-storage diseases is the formation of inclusion bodies (IBs) that are membrane-limited. The nature and function of the IBs has started to be investigated. We have recently found that sequestration of mutated α1-antitrypsin (ATZ) into IBs is a cell protective mechanism that maintains ER function. We also found that IBs are ER-derived and yet separate from the main ER and do not have markers of autophagosomes and lysosomes. We propose that formation of the IBs is a quality control mechanism that leads to storage of unwanted proteins outside the secretory pathway by a mechanism different than direct autophagosome formation from the ER.Addendum to: Granell S, Baldini G, Mohammad S, Nicolin V, Narducci P, Storrie B, Baldini G. Sequestration of mutated Éø-1-antitrypsin into inclusion bodies is a cell protective mechanism to maintain endoplasmic reticulum function. Mol Biol Cell 2008; 19:571-85.