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Alterations in Ca2+ Signalling via ER-Mitochondria Contact Site Remodelling in Cancer

  • Martijn Kerkhofs
  • Carlotta Giorgi
  • Saverio Marchi
  • Bruno Seitaj
  • Jan B. Parys
  • Paolo Pinton
  • Geert Bultynck
  • Mart Bittremieux
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 997)

Abstract

Inter-organellar contact sites establish microdomains for localised Ca2+-signalling events. One of these microdomains is established between the ER and the mitochondria. Importantly, the so-called mitochondria-associated ER membranes (MAMs) contain, besides structural proteins and proteins involved in lipid exchange, several Ca2+-transport systems, mediating efficient Ca2+ transfer from the ER to the mitochondria. These Ca2+ signals critically control several mitochondrial functions, thereby impacting cell metabolism, cell death and survival, proliferation and migration. Hence, the MAMs have emerged as critical signalling hubs in physiology, while their dysregulation is an important factor that drives or at least contributes to oncogenesis and tumour progression. In this book chapter, we will provide an overview of the role of the MAMs in cell function and how alterations in the MAM composition contribute to oncogenic features and behaviours.

Keywords

Calcium signaling Ca2+-transport systems IP3 receptors Voltage-dependent anion channels Chaperones Cell death and survival Mitochondrial bioenergetics Autophagy Mitochondria-associated ER membranes (MAMs) Cancer 

Notes

Acknowledgements

GB and JBP are supported by grants from the Research Foundation - Flanders (FWO) (grants G.0571.12N, G.0819.13N, G.0C91.14N, G.0927.15N and G.0A34.16N) and the Research Council - KU Leuven (OT14/101). MB and MK are holders of a Ph.D. Fellowship from the FWO. P.P. is grateful to Camilla degli Scrovegni for continuous support. P.P. is supported by Telethon (GGP15219/B), the Italian Association for Cancer Research (AIRC) (IG-14442), the Italian Cystic Fibrosis Research Foundation (19/2014), the Italian Ministry of Education, University and Research (COFIN no. 20129JLHSY_002, FIRB no. RBAP11FXBC_002 and Futuro in Ricerca no. RBFR10EGVP_001), local funds from the University of Ferrara and the Italian Ministry of Health. C.G is supported by AIRC (MFAG-13521), the Italian Ministry of Health, Cariplo and local funds from the University of Ferrara.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Martijn Kerkhofs
    • 1
  • Carlotta Giorgi
    • 2
  • Saverio Marchi
    • 2
  • Bruno Seitaj
    • 1
  • Jan B. Parys
    • 1
  • Paolo Pinton
    • 2
  • Geert Bultynck
    • 1
  • Mart Bittremieux
    • 1
  1. 1.Laboratory Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut (LKI)KU LeuvenLeuvenBelgium
  2. 2.Laboratory for Technologies of Advanced Therapies (LTTA), Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental BiologyUniversity of FerraraFerraraItaly

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