Photoreceptor mitochondria and Ca2+ Dynamics

光感受器线粒体和 Ca2 动力学

• 批准号: 9003557
• 负责人: Susan E Brockerhoff
• 金额: $ 42.3万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 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/9003557
• 关键词: Acetylation; Acylation; Afferent Neurons; Biochemical; Biochemical Process; Biochemistry; 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; Neurotransmitters; Organelles; Outcome; Oxidation-Reduction; Photoreceptors; Phototransduction; Post-Translational Protein Processing; Presynaptic Terminals; Process; Proteins; Pump; Recovery; Regulation; Retina; Retinal Cone; Retinal Diseases; Role; Signal Transduction; Zebrafish; controlled release; energy balance; in vivo imaging; meetings; mitochondrial metabolism; prevent; public health relevance

 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).