PUBLICATION

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

Authors
Bisbach, C.M., Hutto, R.A., Poria, D., Cleghorn, W.M., Abbas, F., Vinberg, F., Kefalov, V.J., Hurley, J.B., Brockerhoff, S.E.
ID
ZDB-PUB-201002-211
Date
2020
Source
Scientific Reports   10: 16041 (Journal)
Registered Authors
Abbas, Fatima, Brockerhoff, Susan, Hurley, James B.
Keywords
none
MeSH Terms
  • Mice
  • Photoreceptor Cells/metabolism
  • Mice, Inbred C57BL
  • Calcium Channels/genetics
  • Calcium Channels/metabolism*
  • Calcium Channels/physiology
  • Calcium/metabolism
  • Mitochondrial Membrane Transport Proteins/metabolism
  • Animals
  • Male
  • Female
  • Retinal Rod Photoreceptor Cells/metabolism*
  • Retinal Cone Photoreceptor Cells/metabolism*
  • Biological Transport
  • Mitochondria/metabolism
  • Mitochondria/physiology
  • Mice, Knockout
  • Sodium-Calcium Exchanger/genetics
  • Sodium-Calcium Exchanger/metabolism
  • Zebrafish Proteins/metabolism
  • Zebrafish/metabolism
(all 21)
PubMed
32994451 Full text @ Sci. Rep.
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.
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Citation
Bisbach, C.M., Hutto, R.A., Poria, D., Cleghorn, W.M., Abbas, F., Vinberg, F., Kefalov, V.J., Hurley, J.B., Brockerhoff, S.E. (2020) Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria. Scientific Reports. 10:16041.