Ero1α regulates Ca 2+ fluxes at the endoplasmic reticulum-mitochondria interface (MAM)

Tiziana Anelli, Leda Bergamelli, Eva Margittai, Alessandro Rimessi, Claudio Fagioli, Antonio Malgaroli, Paolo Pinton, Maddalena Ripamonti, Rosario Rizzuto, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

Aims: The endoplasmic reticulum (ER) is involved in many functions, including protein folding, redox homeostasis, and Ca 2+ storage and signaling. To perform these multiple tasks, the ER is composed of distinct, specialized subregions, amongst which mitochondrial-associated ER membranes (MAM) emerge as key signaling hubs. How these multiple functions are integrated with one another in living cells remains unclear. Results: Here we show that Ero1α, a key controller of oxidative folding and ER redox homeostasis, is enriched in MAM and regulates Ca 2+ fluxes. Downregulation of Ero1α by RNA interference inhibits mitochondrial Ca 2+ fluxes and modifies the activity of mitochondrial Ca 2+ uniporters. The overexpression of redox active Ero1α increases passive Ca 2+ efflux from the ER, lowering [Ca 2+] ER and mitochondrial Ca 2+ fluxes in response to IP3 agonists. Innovation: The unexpected observation that Ca 2+ fluxes are affected by either increasing or decreasing the levels of Ero1α reveals a pivotal role for this oxidase in the early secretory compartment and implies a strict control of its amounts. Conclusions: Taken together, our results indicate that the levels, subcellular localization, and activity of Ero1α coordinately regulate Ca 2+ and redox homeostasis and signaling in the early secretory compartment. Antioxid. Redox Signal.

Original languageEnglish
Pages (from-to)1077-1087
Number of pages11
JournalAntioxidants and Redox Signaling
Volume16
Issue number10
DOIs
Publication statusPublished - May 15 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

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    Anelli, T., Bergamelli, L., Margittai, E., Rimessi, A., Fagioli, C., Malgaroli, A., Pinton, P., Ripamonti, M., Rizzuto, R., & Sitia, R. (2012). Ero1α regulates Ca 2+ fluxes at the endoplasmic reticulum-mitochondria interface (MAM). Antioxidants and Redox Signaling, 16(10), 1077-1087. https://doi.org/10.1089/ars.2011.4004