Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria

Abstract Rods and cones use intracellular Ca2+ to regulate many functions, including phototransduction and neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought to be the primary pathway for Ca2+ entry into mitochondria in eukaryotes. We investigate the hypothesis that mito...

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Autores principales:	Celia M. Bisbach, Rachel A. Hutto, Deepak Poria, Whitney M. Cleghorn, Fatima Abbas, Frans Vinberg, Vladimir J. Kefalov, James B. Hurley, Susan E. Brockerhoff
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19fb921ccc8343ada232a66140021e5f
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spelling	oai:doaj.org-article:19fb921ccc8343ada232a66140021e5f2021-12-02T18:51:28ZMitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria10.1038/s41598-020-72708-x2045-2322https://doaj.org/article/19fb921ccc8343ada232a66140021e5f2020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-72708-xhttps://doaj.org/toc/2045-2322Abstract Rods and cones use intracellular Ca2+ to regulate many functions, including phototransduction and neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought to be the primary pathway for Ca2+ entry into mitochondria in eukaryotes. We investigate the hypothesis that mitochondrial Ca2+ uptake via MCU influences phototransduction and energy metabolism in photoreceptors using a mcu -/- zebrafish and a rod photoreceptor-specific Mcu -/- mouse. Using genetically encoded Ca2+ sensors to directly examine Ca2+ uptake in zebrafish cone mitochondria, we found that loss of MCU reduces but does not eliminate mitochondrial Ca2+ uptake. Loss of MCU does not lead to photoreceptor degeneration, mildly affects mitochondrial metabolism, and does not alter physiological responses to light, even in the absence of the Na+/Ca2+, K+ exchanger. Our results reveal that MCU is dispensable for vertebrate photoreceptor function, consistent with its low expression and the presence of an alternative pathway for Ca2+ uptake into photoreceptor mitochondria.Celia M. BisbachRachel A. HuttoDeepak PoriaWhitney M. CleghornFatima AbbasFrans VinbergVladimir J. KefalovJames B. HurleySusan E. BrockerhoffNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-19 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Celia M. Bisbach Rachel A. Hutto Deepak Poria Whitney M. Cleghorn Fatima Abbas Frans Vinberg Vladimir J. Kefalov James B. Hurley Susan E. Brockerhoff Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria
description	Abstract Rods and cones use intracellular Ca2+ to regulate many functions, including phototransduction and neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought to be the primary pathway for Ca2+ entry into mitochondria in eukaryotes. We investigate the hypothesis that mitochondrial Ca2+ uptake via MCU influences phototransduction and energy metabolism in photoreceptors using a mcu -/- zebrafish and a rod photoreceptor-specific Mcu -/- mouse. Using genetically encoded Ca2+ sensors to directly examine Ca2+ uptake in zebrafish cone mitochondria, we found that loss of MCU reduces but does not eliminate mitochondrial Ca2+ uptake. Loss of MCU does not lead to photoreceptor degeneration, mildly affects mitochondrial metabolism, and does not alter physiological responses to light, even in the absence of the Na+/Ca2+, K+ exchanger. Our results reveal that MCU is dispensable for vertebrate photoreceptor function, consistent with its low expression and the presence of an alternative pathway for Ca2+ uptake into photoreceptor mitochondria.
format	article
author	Celia M. Bisbach Rachel A. Hutto Deepak Poria Whitney M. Cleghorn Fatima Abbas Frans Vinberg Vladimir J. Kefalov James B. Hurley Susan E. Brockerhoff
author_facet	Celia M. Bisbach Rachel A. Hutto Deepak Poria Whitney M. Cleghorn Fatima Abbas Frans Vinberg Vladimir J. Kefalov James B. Hurley Susan E. Brockerhoff
author_sort	Celia M. Bisbach
title	Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria
title_short	Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria
title_full	Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria
title_fullStr	Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria
title_full_unstemmed	Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria
title_sort	mitochondrial calcium uniporter (mcu) deficiency reveals an alternate path for ca2+ uptake in photoreceptor mitochondria
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/19fb921ccc8343ada232a66140021e5f
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Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria

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