|ZFIN ID: ZDB-PUB-190803-8|
Increasing Ca2+ in photoreceptor mitochondria alters metabolites, accelerates photoresponse recovery, and reveals adaptations to mitochondrial stress
Hutto, R.A., Bisbach, C.M., Abbas, F., Brock, D.C., Cleghorn, W.M., Parker, E.D., Bauer, B.H., Ge, W., Vinberg, F., Hurley, J.B., Brockerhoff, S.E.
|Source:||Cell death and differentiation 27(3): 1067-1085 (Journal)|
|Registered Authors:||Abbas, Fatima, Brockerhoff, Susan, Hurley, James B.|
|PubMed:||31371786 Full text @ Cell Death Differ.|
Hutto, R.A., Bisbach, C.M., Abbas, F., Brock, D.C., Cleghorn, W.M., Parker, E.D., Bauer, B.H., Ge, W., Vinberg, F., Hurley, J.B., Brockerhoff, S.E. (2019) Increasing Ca2+ in photoreceptor mitochondria alters metabolites, accelerates photoresponse recovery, and reveals adaptations to mitochondrial stress. Cell death and differentiation. 27(3):1067-1085.
ABSTRACTPhotoreceptors are specialized neurons that rely on Ca2+ to regulate phototransduction and neurotransmission. Photoreceptor dysfunction and degeneration occur when intracellular Ca2+ homeostasis is disrupted. Ca2+ homeostasis is maintained partly by mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which can influence cytosolic Ca2+ 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 Ca2+ 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 Ca2+ and disruptions to mitochondrial ultrastructure until late adulthood. We exploited the survival of MCU overexpressing cones to additionally demonstrate that mitochondrial Ca2+ uptake alters the distributions of citric acid cycle intermediates and accelerates recovery kinetics of the cone response to light. Cones adapt to mitochondrial Ca2+ stress by decreasing MICU3, an enhancer of MCU-mediated Ca2+ uptake, and selectively transporting damaged mitochondria away from the ellipsoid toward the synapse. Our findings demonstrate how mitochondrial Ca2+ can influence physiological and metabolic processes in cones and highlight the remarkable ability of cone photoreceptors to adapt to mitochondrial stress.
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