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 language | English |
|---|---|
| Pages (from-to) | 1077-1087 |
| Number of pages | 11 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 16 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - May 15 2012 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Physiology
- Clinical Biochemistry
Cite this
Ero1α regulates Ca 2+ fluxes at the endoplasmic reticulum-mitochondria interface (MAM). / Anelli, Tiziana; Bergamelli, Leda; Margittai, Eva; Rimessi, Alessandro; Fagioli, Claudio; Malgaroli, Antonio; Pinton, Paolo; Ripamonti, Maddalena; Rizzuto, Rosario; Sitia, Roberto.
In: Antioxidants and Redox Signaling, Vol. 16, No. 10, 15.05.2012, p. 1077-1087.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ero1α regulates Ca 2+ fluxes at the endoplasmic reticulum-mitochondria interface (MAM)
AU - Anelli, Tiziana
AU - Bergamelli, Leda
AU - Margittai, Eva
AU - Rimessi, Alessandro
AU - Fagioli, Claudio
AU - Malgaroli, Antonio
AU - Pinton, Paolo
AU - Ripamonti, Maddalena
AU - Rizzuto, Rosario
AU - Sitia, Roberto
PY - 2012/5/15
Y1 - 2012/5/15
N2 - 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.
AB - 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.
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U2 - 10.1089/ars.2011.4004
DO - 10.1089/ars.2011.4004
M3 - Article
C2 - 21854214
AN - SCOPUS:84859232387
VL - 16
SP - 1077
EP - 1087
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 10
ER -