TY - JOUR
T1 - Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria
AU - Bisbach, Celia M.
AU - Hutto, Rachel A.
AU - Poria, Deepak
AU - Cleghorn, Whitney M.
AU - Abbas, Fatima
AU - Vinberg, Frans
AU - Kefalov, Vladimir J.
AU - Hurley, James B.
AU - Brockerhoff, Susan E.
N1 - Funding Information:
We would like to thank Stanley Kim from the South Lake Union Aquatics Core for assisting in maintaining our zebrafish colony. Work in the lab of S.B. was funded by NIH Grants EY026020 and EY028645. Work in the lab of J.B.H. was funded by NIH Grants EY06641 and EY017863. Work in the lab of V.J.K. was funded by NIH Grants EY027387 and EY026675; EY02687 to Washington University, Department of Ophthalmology and Visual Sciences, and by Research to Prevent Blindness. C.M.B. received funding from the NIH Grant F31EY031165. Work in the lab of FV was funded by NEI Grant EY026651, a Research to Prevent Blindness Dr. H. James and Carole Free Career Development Award, and an unrestricted grant from Research to Prevent Blindness (to the Department of Ophthalmology and Visual Sciences at the University of Utah).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85091719150&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-72708-x
DO - 10.1038/s41598-020-72708-x
M3 - Article
C2 - 32994451
AN - SCOPUS:85091719150
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 16041
ER -