Journal of Biological Chemistry
Volume 287, Issue 17, 20 April 2012, Pages 14088-14098
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Cell Biology
Chronic Expression of RCAN1-1L Protein Induces Mitochondrial Autophagy and Metabolic Shift from Oxidative Phosphorylation to Glycolysis in Neuronal Cells*

https://doi.org/10.1074/jbc.M111.305342Get rights and content
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Expression of the RCAN1 gene can be induced by multiple stresses. RCAN1 proteins (RCAN1s) have both protective and harmful effects and are implicated in common human pathologies. The mechanisms by which RCAN1s function, however, remain poorly understood. We identify RCAN1s as regulators of mitochondrial autophagy (mitophagy) and demonstrate that induction of RCAN1-1L can cause dramatic degradation of mitochondria. The mechanisms of such degradation involve the adenine nucleotide translocator and mitochondrial permeability transition pore opening. We also demonstrate that RCAN1-1L induction can shift cellular bioenergetics from aerobic respiration to glycolysis, yet RCAN1-1L has very little effect on cell division, whereas it has a cumulative negative effect on cell survival. These results shed the light on mechanisms by which RCAN1s can protect or harm cells and by which they may operate in human pathologies. They also suggest that RCAN1s are important players in autophagy and such elusive phenomena as the mitochondrial permeability transition pore.

Autophagy
Metabolism
Mitochondria
Neurodegeneration
Stress
RCAN1

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*

This work was supported, in whole or in part, by National Institutes of Health Grants RO1-ES003598 (and American Recovery and Reinvestment Act supplement 3RO1-ES 003598-22S2) (to K. J. A. D.) and R01AG016718 (to E. C.).

This article contains supplemental Figs. 1–4.