Open AccessIncreasing Ca2+ in photoreceptor mitochondria alters metabolites, accelerates photoresponse recovery, and reveals adaptations to mitochondrial stress
Author(s) -
Rachel Hutto,
Celia M Bisbach,
Fatima Hashim Abbas,
Daniel C Brock,
Whitney M. Cleghorn,
Edward D Parker,
Benjamin H Bauer,
William Ge,
Frans Vinberg,
James B. Hurley
Publication year - 2019
Publication title -
cell death and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.348
H-Index - 218
eISSN - 1476-5403
pISSN - 1350-9047
DOI - 10.1038/s41418-019-0398-2
Subject(s) - mitochondrion , uniporter , visual phototransduction , cytosol , biology , microbiology and biotechnology , oxidative stress , retina , biochemistry , neuroscience , enzyme
Photoreceptors are specialized neurons that rely on Ca 2+ to regulate phototransduction and neurotransmission. Photoreceptor dysfunction and degeneration occur when intracellular Ca 2+ homeostasis is disrupted. Ca 2+ homeostasis is maintained partly by mitochondrial Ca 2+ uptake through the mitochondrial Ca 2+ uniporter (MCU), which can influence cytosolic Ca 2+ signals, stimulate energy production, and trigger apoptosis. Here we discovered that zebrafish cone photoreceptors express unusually low levels of MCU. We expected that this would be important to prevent mitochondrial Ca 2+ overload and consequent cone degeneration. To test this hypothesis, we generated a cone-specific model of MCU overexpression. Surprisingly, we found that cones tolerate MCU overexpression, surviving elevated mitochondrial Ca 2+ and disruptions to mitochondrial ultrastructure until late adulthood. We exploited the survival of MCU overexpressing cones to additionally demonstrate that mitochondrial Ca 2+ uptake alters the distributions of citric acid cycle intermediates and accelerates recovery kinetics of the cone response to light. Cones adapt to mitochondrial Ca 2+ stress by decreasing MICU3, an enhancer of MCU-mediated Ca 2+ uptake, and selectively transporting damaged mitochondria away from the ellipsoid toward the synapse. Our findings demonstrate how mitochondrial Ca 2+ can influence physiological and metabolic processes in cones and highlight the remarkable ability of cone photoreceptors to adapt to mitochondrial stress.