Journal ArticleDOI
Ero1α regulates Ca(2+) fluxes at the endoplasmic reticulum-mitochondria interface (MAM).
Tiziana Anelli,Leda Bergamelli,Éva Margittai,Alessandro Rimessi,Claudio Fagioli,Antonio Malgaroli,Paolo Pinton,Maddalena Ripamonti,Rosario Rizzuto,Roberto Sitia +9 more
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TLDR
The 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.Abstract:
Aims: The endoplasmic reticulum (ER) is involved in many functions, including protein folding, redox homeostasis, and Ca2+ 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 Ca2+ fluxes. Downregulation of Ero1α by RNA interference inhibits mitochondrial Ca2+ fluxes and modifies the activity of mitochondrial Ca2+ uniporters. The overexpression of redox active Ero1α increases passive Ca2+ efflux from the ER, lowering [Ca2+]ER and mitochondrial Ca2+ fluxes in response to IP3 agonists. Innovation: The unexpected observation that Ca2+ fluxes are affected by either increasing or decreasing the levels of Ero1α reveals a pivotal role for...read more
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Journal ArticleDOI
Reactive Oxygen Species in Metabolic and Inflammatory Signaling.
TL;DR: The role of ROS in the regulation metabolic/inflammatory diseases including atherosclerosis, diabetes mellitus, and stroke is highlighted and the balance ROS signaling plays in both physiology and pathophysiology is understood.
Journal ArticleDOI
PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress
Tom Verfaillie,N Rubio,N Rubio,Abhishek D. Garg,Geert Bultynck,Rosario Rizzuto,Jean-Paul Decuypere,Jacques Piette,Linehan C,Sanjeev Gupta,Afshin Samali,Patrizia Agostinis +11 more
TL;DR: It is revealed that PERK (RNA-dependent protein kinase (PKR)-like ER kinase), a key ER stress sensor of the unfolded protein response, is uniquely enriched at the mitochondria-associated ER membranes (MAMs), suggesting that loss of PERK may cause defects in cell death sensitivity in pathological conditions linked to ROS-mediated ER stress.
Journal ArticleDOI
Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1.
Olga A. Smirnova,Olga N. Ivanova,Birke Bartosch,Vladimir T. Valuev-Elliston,Furkat Mukhtarov,Sergey N. Kochetkov,Alexander V. Ivanov +6 more
TL;DR: The data show that NS5A protein induces oxidative stress by several multistep mechanisms and contributes to ROS production by activating expression of NADPH oxidases 1 and 4 as well as cytochrome P450 2E1.
Journal ArticleDOI
Where the endoplasmic reticulum and the mitochondrion tie the knot: the mitochondria-associated membrane (MAM).
Arun Raturi,Thomas Simmen +1 more
TL;DR: These exciting findings demonstrate that the physiological interactions between the ER and mitochondria are so bilateral that the relationship is tempted to compare their relationship to the one of a married couple: distinct, but inseparable and certainly dependent on each other.
Journal ArticleDOI
Endoplasmic Reticulum–Mitochondrial Contactology: Structure and Signaling Functions
TL;DR: The structure of the ER-mito contacts, methods for studying them, and the roles of contacts in Ca2+ and reactive oxygen species (ROS) signaling are reviewed.
References
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Journal ArticleDOI
Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease
TL;DR: The endoplasmic reticulum is the major site in the cell for protein folding and trafficking and is central to many cellular functions and is emerging as a potential site for the intersection of inflammation and metabolic disease.
Journal ArticleDOI
Close Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca2+ Responses
Rosario Rizzuto,Paolo Pinton,Paolo Pinton,Walter A. Carrington,Walter A. Carrington,Frederic S. Fay,Frederic S. Fay,Kevin E. Fogarty,Kevin E. Fogarty,Lawrence M. Lifshitz,Lawrence M. Lifshitz,Richard A. Tuft,Richard A. Tuft,Tullio Pozzan,Tullio Pozzan +14 more
TL;DR: The spatial relation between mitochondria and endoplasmic reticulum in living HeLa cells was analyzed at high resolution in three dimensions with two differently colored, specifically targeted green fluorescent proteins to emphasize the importance of cell architecture and the distribution of organelles in regulation of Ca2+ signaling.
Journal ArticleDOI
Redox-based regulation of signal transduction : Principles, pitfalls, and promises
Yvonne M. W. Janssen-Heininger,Brooke T. Mossman,Nicholas H. Heintz,Henry Jay Forman,Balaraman Kalyanaraman,Toren Finkel,Jonathan S. Stamler,Sue Goo Rhee,Albert van der Vliet +8 more
TL;DR: Some of the recent findings that illuminate the significance of redox signaling and exciting future perspectives are reviewed to highlight some of the current pitfalls and the approaches needed to advance this important area of biochemical and biomedical research.
Journal ArticleDOI
Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells.
Mariusz R. Wieckowski,Carlotta Giorgi,Carlotta Giorgi,Magdalena Lebiedzinska,Jerzy Duszyński,Paolo Pinton +5 more
TL;DR: Optimized protocols to isolate mitochondria-associated membranes, containing unique regions of ER membranes attached to the outer mitochondrial membrane and mitochondria without contamination from other organelles are provided.
Journal ArticleDOI
Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins
TL;DR: Hydrogen peroxide accumulates transiently in various cell types stimulated with peptide growth factors and participates in receptor signaling by oxidizing the essential cysteine residues of protein tyrosine phosphatases and the lipid phosphatase PTEN.
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