AI Article Synopsis

  • The mitochondria-associated membrane (MAM) is a specialized area of the endoplasmic reticulum (ER) that helps in the transfer of ions, lipids, and metabolites between the ER and mitochondria.
  • The study reveals that a process called palmitoylation, which involves the attachment of fatty acids to proteins, helps ER-localized proteins like TMX and calnexin to become more concentrated in the MAM.
  • Disrupting palmitoylation through mutations or chemical interference prevents proper positioning of these proteins in the MAM, highlighting the importance of palmitoylation for the function of certain ER proteins.

Article Abstract

The mitochondria-associated membrane (MAM) is a domain of the endoplasmic reticulum (ER) that mediates the exchange of ions, lipids and metabolites between the ER and mitochondria. ER chaperones and oxidoreductases are critical components of the MAM. However, the localization motifs and mechanisms for most MAM proteins have remained elusive. Using two highly related ER oxidoreductases as a model system, we now show that palmitoylation enriches ER-localized proteins on the MAM. We demonstrate that palmitoylation of cysteine residue(s) adjacent to the membrane-spanning domain promotes MAM enrichment of the transmembrane thioredoxin family protein TMX. In addition to TMX, our results also show that calnexin shuttles between the rough ER and the MAM depending on its palmitoylation status. Mutation of the TMX and calnexin palmitoylation sites and chemical interference with palmitoylation disrupt their MAM enrichment. Since ER-localized heme oxygenase-1, but not cytosolic GRP75 require palmitoylation to reside on the MAM, our findings identify palmitoylation as key for MAM enrichment of ER membrane proteins.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261551PMC
http://dx.doi.org/10.1038/emboj.2011.384DOI Listing

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Palmitoylated TMX and calnexin target to the mitochondria-associated membrane.

EMBO J

January 2012

Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Article Synopsis
  • The mitochondria-associated membrane (MAM) is a specialized area of the endoplasmic reticulum (ER) that helps in the transfer of ions, lipids, and metabolites between the ER and mitochondria.
  • The study reveals that a process called palmitoylation, which involves the attachment of fatty acids to proteins, helps ER-localized proteins like TMX and calnexin to become more concentrated in the MAM.
  • Disrupting palmitoylation through mutations or chemical interference prevents proper positioning of these proteins in the MAM, highlighting the importance of palmitoylation for the function of certain ER proteins.
View Article and Find Full Text PDF

In the endoplasmic reticulum (ER), a variety of oxidoreductases classified in the thioredoxin superfamily have been found to catalyze the formation and rearrangement of disulfide bonds. However, the precise function and specificity of the individual thioredoxin family proteins remain to be elucidated. Here, we characterize a transmembrane thioredoxin-related protein (TMX), a membrane-bound oxidoreductase in the ER.

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Various proteins sharing thioredoxin (Trx)-like active site sequences (Cys-Xxx-Xxx-Cys) have been found and classified in the Trx superfamily. Among them, transmembrane Trx-related protein (TMX) was recently identified as a novel protein possessing an atypical active site sequence, Cys-Pro-Ala-Cys. In the present study, we describe the properties of this membranous Trx-related molecule.

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