Rab32 modulates apoptosis onset and Mitochondria-associated Membrane (MAM) properties

Michael Bui, Susanna Y. Gilady, Ross E B Fitzsimmons, Matthew D. Benson, Emily M. Lynes, Kevin Gesson, Neal M. Alto, Stefan Strack, John D. Scott, Thomas Simmen

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101 Scopus citations

Abstract

The mitochondria-associated membrane (MAM) has emerged as an endoplasmic reticulum (ER) signaling hub that accommodates ER chaperones, including the lectin calnexin. At the MAM, these chaperones control ER homeostasis but also play a role in the onset of ER stress-mediated apoptosis, likely through the modulation of ER calcium signaling. These opposing roles of MAM-localized chaperones suggest the existence of mechanisms that regulate the composition and the properties of ER membrane domains. Our results now show that the GTPase Rab32 localizes to the ER and mitochondria, and we identify this protein as a regulator of MAM properties. Consistent with such a role, Rab32 modulates ER calcium handling and disrupts the specific enrichment of calnexin on the MAM,while not affecting the ER distribution of protein-disulfide isomerase and mitofusin-2. Furthermore, Rab32 determines the targeting ofPKAto mitochondrial and ER membranes and through its overexpression or inactivation increases the phosphorylation of Bad and of Drp1. Through a combination of its functions as a PKA-anchoring protein and a regulator of MAM properties, the activity and expression level of Rab32 determine the speed of apoptosis onset.

Original languageEnglish (US)
Pages (from-to)31590-31602
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number41
DOIs
StatePublished - Oct 8 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bui, M., Gilady, S. Y., Fitzsimmons, R. E. B., Benson, M. D., Lynes, E. M., Gesson, K., Alto, N. M., Strack, S., Scott, J. D., & Simmen, T. (2010). Rab32 modulates apoptosis onset and Mitochondria-associated Membrane (MAM) properties. Journal of Biological Chemistry, 285(41), 31590-31602. https://doi.org/10.1074/jbc.M110.101584