Cell type-specific role of Src kinase in brain mitochondrial metabolism and behavior

Src 激酶在脑线粒体代谢和行为中的细胞类型特异性作用

• 批准号: RGPIN-2022-03945
• 负责人: HebertChatelain, Etienne
• 金额: $ 2.33万
• 依托单位: Université de Moncton
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745011
• 关键词: Cell; type; specific; role; Src

Mitochondria are considered as the power plants of cells, converting nutrients (like carbohydrates and lipids) into cellular energetic fuel. These tiny engines form a network inside the cell, and individual mitochondria can divide, or fuse together to become either smaller or elongated. The shape of mitochondria has a great impact on their capacity to generate energy. There are multiple mechanisms to control the shape of mitochondria and adapt them to cellular needs. We discovered that a protein named Src can change the shape and activity of mitochondria. We will examine how this protein impacts on the morphology and activity of the cellular power plant. The capacity of mitochondria to produce energy is crucial for the brain. This organ consumes approximately 25% of the total body energy, although its mass only represents 2% of the total body mass. The brain is composed of multiple cell types with different functions, and different circuits among these cells are responsible for the control of specific behaviors. Our recent work has shown that change in mitochondrial activity in specific brain cell types has specific outcomes on the behavior. For instance, decreased mitochondrial activity in neurons (nerve cells able to transmit information in the brain) alters memory. On the other hand, lower mitochondrial activity in astrocytes (cells important for transporting nutrients inside the brain) decreases social interaction. Thus, we will study how the regulation of mitochondrial shape and activity by Src in these brain cell types affects behavior in mice. This research program will reveal how mitochondria adapt to cellular needs, and how the brain controls our behavior. Our work will therefore open new fields in fundamental cell biology and neuroscience.

线粒体被认为是细胞的发电厂，将营养物质（如碳水化合物和脂质）转化为细胞的能量燃料。这些微小的引擎在细胞内形成一个网络，单个线粒体可以分裂或融合在一起，变得更小或更长。线粒体的形状对其产生能量的能力有很大影响。有多种机制来控制线粒体的形状并使其适应细胞的需要。我们发现一种名为Src的蛋白质可以改变线粒体的形状和活性。我们将研究这种蛋白质如何影响细胞发电厂的形态和活性。线粒体产生能量的能力对大脑至关重要。这个器官消耗大约25%的身体总能量，尽管它的质量只占身体总质量的2%。大脑由多种功能不同的细胞组成，这些细胞之间的不同回路负责控制特定的行为。我们最近的工作表明，特定脑细胞类型中线粒体活性的变化对行为有特定的影响。例如，神经元（能够在大脑中传递信息的神经细胞）中线粒体活性的降低会改变记忆。另一方面，星形胶质细胞（对大脑内运输营养物质很重要的细胞）中线粒体活性降低会减少社会互动。因此，我们将研究这些脑细胞类型中Src对线粒体形状和活性的调节如何影响小鼠的行为。 这项研究计划将揭示线粒体如何适应细胞的需要，以及大脑如何控制我们的行为。因此，我们的工作将在基础细胞生物学和神经科学中开辟新的领域。