Mitochondrial pyruvate transport regulates presynaptic metabolism and neurotransmission

Glucose has long been considered the primary fuel source for the brain. However, glucose levels fluctuate in the brain during sleep or circuit activity, posing significant metabolic stress. Here, we demonstrate that the mammalian brain utilizes pyruvate as a fuel source, and pyruvate can support neuronal viability in the absence of glucose. Nerve terminals are sites of metabolic vulnerability, and we show that mitochondrial pyruvate uptake is a critical step in oxidative ATP production in hippocampal terminals. We find that the mitochondrial pyruvate carrier is post-translationally modified by lysine acetylation which in turn modulates mitochondrial pyruvate uptake. Our data reveal that the mitochondrial pyruvate carrier regulates distinct steps in neurotransmission, namely, the spatiotemporal pattern of synaptic vesicle release and the efficiency of vesicle retrieval, functions that have profound implications for synaptic plasticity. In summary, we identify pyruvate as a potent neurona..., , , # Mitochondrial pyruvate transport regulates presynaptic metabolism and neurotransmission

Anupama Tiwari, Jongyun Myeong, Arsalan Hashemiaghdam, Marion I. Stunault, Hao Zhang, Xianfeng Niu, Marissa A. Laramie, Jasmin Sponagel, Leah Shriver, Gary J. Patti, Vitaly A. Klyachko and Ghazaleh Ashrafi

Correspondence: [[e-mail]](mailto:[e-mail])

[https://doi.org/10.5061/dryad.z8w9ghxnq](https://doi.org/10.5061/dryad.z8w9ghxnq)

## Description of method

All the recorded movies from synapses expressing pHluroin.

\- Tyrode_Lactate_Pyruvate

36 files: each file include multi synapse movies (37x37xtimeframe)

\- Tyrode_Lactate_Pyruvate_UK5099

9 files: each file include multi synapse movies (37x37xtimeframe)

Preprocessing:

VGlut1-pHluorin- release event detection and localization at subpixel resolution were performed using MATLAB and the uTrack software package, which was kindly made available by Dr Gaudenz Danuser’s lab. Localization precision was determined directly fro...

长期以来，葡萄糖被认为是大脑的主要能量来源。然而，睡眠或神经环路活动期间，大脑内葡萄糖水平会出现波动，带来显著的代谢应激。本研究证实，哺乳动物大脑可利用丙酮酸作为能量来源，且在缺乏葡萄糖的情况下，丙酮酸能够维持神经元存活。神经末梢是代谢易损位点，我们的研究显示，线粒体丙酮酸摄取是海马神经末梢氧化ATP生成过程中的关键步骤。我们发现，线粒体丙酮酸载体（mitochondrial pyruvate carrier）会发生赖氨酸乙酰化的翻译后修饰，该修饰可调控线粒体丙酮酸摄取。我们的数据表明，线粒体丙酮酸载体可调控神经传递中的不同环节，具体为突触囊泡释放的时空模式与囊泡回收效率，这些功能对突触可塑性具有重要意义。综上，我们确认丙酮酸是一种高效的神经元……

# 线粒体丙酮酸转运调控突触前代谢与神经传递

Anupama Tiwari, Jongyun Myeong, Arsalan Hashemiaghdam, Marion I. Stunault, Hao Zhang, Xianfeng Niu, Marissa A. Laramie, Jasmin Sponagel, Leah Shriver, Gary J. Patti, Vitaly A. Klyachko and Ghazaleh Ashrafi

通讯作者：[[e-mail]](mailto:[e-mail])

[https://doi.org/10.5061/dryad.z8w9ghxnq](https://doi.org/10.5061/dryad.z8w9ghxnq)

## 方法描述
所有记录的影像均来自表达pHluorin（pH荧光蛋白）的突触样本。
- Tyrode_Lactate_Pyruvate组：共36个数据文件，每个文件包含多组突触影像（格式为37×37×时间帧）
- Tyrode_Lactate_Pyruvate_UK5099组：共9个数据文件，每个文件包含多组突触影像（格式为37×37×时间帧）

### 预处理流程
采用MATLAB软件与uTrack软件包完成VGlut1-pHluorin的释放事件检测与亚像素分辨率下的定位分析，该软件包由Gaudenz Danuser博士实验室无偿提供。定位精度直接通过……（原文未完整给出）