线粒体自噬（mitophagy）是指在活性氧、营养缺乏等刺激下，细胞内损伤的线粒体被特异性包裹进自噬体中，并与溶酶体融合，从而引起损伤线粒体的降解过程。我们的前期工作发现，A型肉毒毒素（BTXA）诱导颌下腺细胞凋亡与自噬时伴有线粒体自噬的发生，然而针对BTXA诱导细胞发生线粒体自噬的研究尚无报道。本项目以BTXA抑制颌下腺分泌为主线，以线粒体自噬为重点，探讨BTXA治疗唾液腺相关性疾病的具体作用和机制。我们拟采用：（1）以大鼠为模型，观察BTXA注射颌下腺时线粒体自噬相关蛋白表达及分布变化情况；(2)在BTXA培养的细胞上观察线粒体膜电位、ROS等变化水平，同时观察NIX,FUNDC1，Parkin，Pink等线粒体自噬相关蛋白的变化情况； (3) 通过小RNA干扰技术选择性敲低或过表达线粒体自噬相关蛋白，在分子水平上明确线粒体自噬的信号转到通路，为BTXA的临床应用提供新思路。

Mitochondiral autophagy, which is also known as Mitophagy, refers to the degradation of damaged mitochondria caused by stimulis such as reactive oxygen species (ROS), nutritional deprivation, etc. Our previous investigations found the existence of apoptosis and autophagy as well as mitophagy of acinar cell involved in botulinum toxin type A (BTXA) treating submandibular gland (SMG). However, the mechanism of BTXA-modulated mitophagy remains unclear. In this study, we try to investigate whether mitophagy occurs to BTXA inhibiting salivary gland.To evaluate the mitophagy occurrence, (1) we first examined that the expression and location of mitophagy related protein in vivo; (2)we examined the change of mitochondrial dysfunction after the treatment of BTXA in the SMG-C6 cell lines, and we also try to investigate the expression of Parkin, Pink, NIX and FUNDC1 in vitro; (3) to investigate the mechanism of BTXA and mitophagy in SMG, RNA interference or overexpression methods will be applied to change the protein levels. This study may provide some new clues to understand the mitophagy in BTXA inhibiting the function of salivary function.