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Nanospaces between endoplasmic reticulum and mitochondria as control centres of pancreatic β-cell metabolism and survival

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Abstract

Nanometre-scale spaces between organelles represent focused nodes for signal transduction and the control of cellular decisions. The endoplasmic reticulum (ER) and the mitochondria form dynamic quasi-synaptic interaction nanodomains in all cell types examined, but the functional role of these junctions in cellular metabolism and cell survival remains to be fully understood. In this paper, we review recent evidence that ER Ca2+ channels, such as the RyR and IP3R, can signal specifically across this nanodomain to the adjacent mitochondria to pace basal metabolism, with focus on the pancreatic β-cell. Blocking these signals in the basal state leads to a form of programmed cell death associated with reduced ATP and the induction of calpain-10 and hypoxia-inducible factors. On the other hand, the hyperactivity of this signalling domain plays a deleterious role during classical forms of apoptosis. Thus, the nanospace between ER and mitochondria represents a critical rheostat controlling both metabolism and programmed cell death. Many aspects of the mechanisms underlying this control system remain to be uncovered, and new nanotechnologies are required understand these domains at a molecular level.

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Acknowledgements

Work in the author’s laboratory is funded by the Canadian Diabetes Association and the Juvenile Diabetes Research Foundation and the Canadian Institutes for Health Research.

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None of the authors have any conflict of interest.

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Authors and Affiliations

  1. Department of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3

    James D. Johnson, Michael J. Bround & Sarah A. White

  2. Department of Surgery, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3

    Dan S. Luciani

  3. Department of Cellular and Physiological Sciences, University of British Columbia, 5358 Life Sciences Building, Vancouver, BC, Canada, V6T 1Z3

    James D. Johnson

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  1. James D. Johnson
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  2. Michael J. Bround
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Correspondence to James D. Johnson.

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Johnson, J.D., Bround, M.J., White, S.A. et al. Nanospaces between endoplasmic reticulum and mitochondria as control centres of pancreatic β-cell metabolism and survival. Protoplasma 249 (Suppl 1), 49–58 (2012). https://doi.org/10.1007/s00709-011-0349-3

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