Palmitoylation targets calnexin to the MAM and regulates its functions

  • Author / Creator
    Lynes, Emily Marian
  • The mitochondria associated membranes (MAMs) of the endoplasmic reticulum (ER) are the points of contact between the ER, which is the organelle responsible for lipid and secreted protein synthesis and calcium storage, and the mitochondria, which are organelles responsible for cellular energy production. The MAM has many roles including the transfer of lipids and metabolites between these two organelles, as well as the mediation of calcium signaling between the ER and mitochondria. Calcium transfer at MAMs is of vital importance as it regulates mitochondrial metabolism and apoptosis, or programmed cell death. Although the MAM has been well-characterized in recent years, very little is currently known about how proteins target there and how these contact sites are maintained. In this thesis, I have identified a novel MAM targeting mechanism, palmitoylation, using a chimeric mutagenesis strategy. I have also identified two proteins, TMX and calnexin, which use this signal to target to MAM. Furthermore, I have characterized the role of calnexin at MAM by overexpressing wildtype and non-palmitoylatable calnexin in calnexin knockout cells. This led to the discovery that calnexin plays a role in ER-mitochondria calcium transfer and may affect structural changes at MAM during cellular stress. These findings have implications for the study of diseases where mitochondrial metabolism and deregulated cell death are factors, for example cancer and neurodegenerative disease.

  • Subjects / Keywords
  • Graduation date
    Spring 2013
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • LaPointe, Paul (Cell Biology)
    • Colberg-Poley, Anamaris (Pediatrics, George Washington University)
    • Hobman, Tom (Cell Biology)
    • Vance, Jean (Medicine)