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
  • Animals
  • Biological Transport
  • Calcium/metabolism
  • Calcium Channels/genetics
  • Calcium Channels/metabolism*
  • Calcium Channels/physiology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria/metabolism
  • Mitochondria/physiology
  • Mitochondrial Membrane Transport Proteins/metabolism
  • Photoreceptor Cells/metabolism
  • Retinal Cone Photoreceptor Cells/metabolism*
  • Retinal Rod Photoreceptor Cells/metabolism*
  • Sodium-Calcium Exchanger/genetics
  • Sodium-Calcium Exchanger/metabolism
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
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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