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Photoreceptor mitochondria and Ca2+ Dynamics

光感受器线粒体和 Ca2 动力学

基本信息

批准号：
9197293
负责人：
Susan E Brockerhoff
金额：
$ 42.26万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9197293
关键词：
Acetylation Acylation Afferent Neurons Biochemical Biochemical Process Biochemistry Calcium Signaling Calcium ion Cell Death Cell Nucleus Cell membrane Cell physiology Cells Cytoplasm Cytosol Defect Disease Endoplasmic Reticulum Energy Metabolism Enzymes Genetic Transcription Goals Individual Investigation Ion Channel Knowledge Ligands Light Link Measures Mediating Mediator of activation protein Metabolism Methods Mitochondria Modification Monitor Neurons Organelles Outcome Oxidation-Reduction Photoreceptors Phototransduction Post-Translational Protein Processing Presynaptic Terminals Process Proteins Pump Recovery Regulation Retina Retinal Cone Retinal Diseases Role Zebrafish cell growth regulation controlled release energy balance in vivo imaging ion dynamics mitochondrial metabolism neurotransmitter release prevent public health relevance

项目摘要

DESCRIPTION (provided by applicant): Intracellular crosstalk mediated by calcium ions (Ca2+) is fundamentally important for understanding regulation of cellular function. Cellular Ca2+ fluxes and mitochondrial Ca2+ dynamics, influence the activity of mitochondrial enzymes involved in energy metabolism and cellular redox. These changes influence post-translational modification of proteins in mitochondria, the cytoplasm and the nucleus, which control cell functions such as energy metabolism and transcription. We hypothesize that Ca2+ signaling by mitochondria in photoreceptors is critical for their function and survival. The study proposed here will define how photoreceptor activity is regulated by mitochondrial Ca2+ to meet the specialized demands of this unique sensory neuron. Using genetically encoded Ca2+ indicators and in vivo imaging, we have documented large Ca2+ fluctuations in the cell bodies and mitochondria of zebrafish cone photoreceptors. We also developed methods for manipulating Ca2+ in cell bodies and mitochondria and for detecting protein modifications and cellular redox changes. We will use these methods to determine how Ca2+ fluxes within photoreceptors are processed by mitochondria. We will study how mitochondria regulate Ca2+ in photoreceptor cell bodies and the role of the mitochondrial Ca2+ uniporter (Aim 1). We also will determine how Ca2+ controls the cytoplasmic redox potential and acylation of proteins (Aim 2).

描述（由申请人提供）：钙离子（Ca2+）介导的细胞内串扰对于理解细胞功能的调节至关重要。细胞内Ca2+通量和线粒体内Ca2+动力学影响着参与能量代谢和细胞氧化还原的线粒体酶的活性。这些变化影响线粒体、细胞质和细胞核中蛋白质的翻译后修饰，这些蛋白质控制细胞功能，如能量代谢和转录。我们推测，光感受器中线粒体的Ca2+信号传导对其功能和存活至关重要。本文提出的研究将定义感光细胞活性如何受线粒体Ca2+的调节，以满足这种独特的感觉神经元的特殊需求。使用遗传编码的Ca2+指标和体内成像，我们已经记录了大的Ca2+波动的细胞体和线粒体的斑马鱼视锥光感受器。我们还开发了用于操纵细胞体和线粒体中的Ca2+以及用于检测蛋白质修饰和细胞氧化还原变化的方法。我们将使用这些方法来确定光感受器内的Ca2+通量如何被线粒体处理。我们将研究线粒体如何调节感光细胞体中的Ca2+和线粒体Ca2+单向转运体的作用（目的1）。我们还将确定Ca2+如何控制细胞质氧化还原电位和蛋白质酰化（目的2）。