The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial function

V Padovano, IY Kuo, LK Stavola, HR Aerni, BJ Flaherty, HC Chapin, M Ma, S Somlo, A Boletta, BE Ehrlich, J Rinehart, MJ Caplan

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Abstract

Autosomal dominant polycystic kidney disease is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which form an ion channel complex that may mediate ciliary sensory processes and regulate endoplasmic reticulum (ER) Ca2+ release. Loss of PC1 expression profoundly alters cellular energy metabolism. The mechanisms that control the trafficking of PC1 and PC2, as well as their broader physiological roles, are poorly understood. We found that O2 levels regulate the subcellular localization and channel activity of the polycystin complex through its interaction with the O2-sensing prolyl hydroxylase domain containing protein EGLN3 (or PHD3), which hydroxylates PC1. Moreover, cells lacking PC1 expression use less O2 and show less mitochondrial Ca2+ uptake in response to bradykinin-induced ER Ca2+ release, indicating that PC1 can modulate mitochondrial function. These data suggest a novel role for the polycystins in sensing and responding to cellular O2 levels. © 2017 Padovano et al.
Original languageEnglish
Pages (from-to)261-269
Number of pages9
JournalMolecular Biology of the Cell
Volume28
Issue number2
DOIs
Publication statusPublished - 2017

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TRPP Cation Channels
Oxygen
Endoplasmic Reticulum
Prolyl Hydroxylases
Autosomal Dominant Polycystic Kidney
Bradykinin
Ion Channels
Energy Metabolism
polycystic kidney disease 1 protein
Mutation

Cite this

Padovano, V., Kuo, IY., Stavola, LK., Aerni, HR., Flaherty, BJ., Chapin, HC., ... Caplan, MJ. (2017). The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial function. Molecular Biology of the Cell, 28(2), 261-269. https://doi.org/10.1091/mbc.E16-08-0597

The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial function. / Padovano, V; Kuo, IY; Stavola, LK; Aerni, HR; Flaherty, BJ; Chapin, HC; Ma, M; Somlo, S; Boletta, A; Ehrlich, BE; Rinehart, J; Caplan, MJ.

In: Molecular Biology of the Cell, Vol. 28, No. 2, 2017, p. 261-269.

Research output: Contribution to journalArticle

Padovano, V, Kuo, IY, Stavola, LK, Aerni, HR, Flaherty, BJ, Chapin, HC, Ma, M, Somlo, S, Boletta, A, Ehrlich, BE, Rinehart, J & Caplan, MJ 2017, 'The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial function', Molecular Biology of the Cell, vol. 28, no. 2, pp. 261-269. https://doi.org/10.1091/mbc.E16-08-0597
Padovano, V ; Kuo, IY ; Stavola, LK ; Aerni, HR ; Flaherty, BJ ; Chapin, HC ; Ma, M ; Somlo, S ; Boletta, A ; Ehrlich, BE ; Rinehart, J ; Caplan, MJ. / The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial function. In: Molecular Biology of the Cell. 2017 ; Vol. 28, No. 2. pp. 261-269.
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AB - Autosomal dominant polycystic kidney disease is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which form an ion channel complex that may mediate ciliary sensory processes and regulate endoplasmic reticulum (ER) Ca2+ release. Loss of PC1 expression profoundly alters cellular energy metabolism. The mechanisms that control the trafficking of PC1 and PC2, as well as their broader physiological roles, are poorly understood. We found that O2 levels regulate the subcellular localization and channel activity of the polycystin complex through its interaction with the O2-sensing prolyl hydroxylase domain containing protein EGLN3 (or PHD3), which hydroxylates PC1. Moreover, cells lacking PC1 expression use less O2 and show less mitochondrial Ca2+ uptake in response to bradykinin-induced ER Ca2+ release, indicating that PC1 can modulate mitochondrial function. These data suggest a novel role for the polycystins in sensing and responding to cellular O2 levels. © 2017 Padovano et al.

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