Mitochondrial dysfunction is proposed to be substantially associated with ageing and ageing-related diseases like Alzheimer’s disease (AD). However, it is unclear whether different mouse models with mitochondrial-related diseases have similar changes in mitochondrial morphology of the same tissues. Moreover, whether similarities in mitochondrial morphology can be a suitable marker for screening and/or discovering mitochondrial-protective substances remains unknown. Mitochondria morphology in different tissues of a novel mitochondrial outer membrane protein Slc25a46 knockout mouse and a traditional APP_SWE/PS1ΔE9 transgenic mouse were examined using transmission electron microscope (TEM). Both young Slc25a46 knockout mice and aged APP_SWE/PS1ΔE9 mice models showed similar mitochondrial damage in cerebellum tissues. The results indicated that different mitochondrial-related diseases shared similar alteration and defects in mitochondrial morphology. Furthermore, Lycium ruthenicum Murr. extract, a bioactive food substance with cognition-improving property, could effectively improve muscle strength and increase body weight in the Slc25a46 knockout mice. These findings suggest that mitochondrial morphology defects in mice models, particularly in the mitochondrial compartment, represent a unified and effective marker for screening and validating natural product-derived functional substances with mitochondrial protective properties. It also holds potential application in mitochondrial-impaired senile neurodegenerative diseases, especially in AD.

线粒体功能障碍被认为与衰老和衰老相关疾病如阿尔茨海默病 (AD) 密切相关。然而，尚不清楚患有线粒体相关疾病的不同小鼠模型是否具有相同组织的线粒体形态学的相似变化。此外，线粒体形态的相似性是否可以作为筛选和/或发现线粒体保护物质的合适标记仍然未知。使用透射电子显微镜 (TEM) 检查新型线粒体外膜蛋白Slc25a46敲除小鼠和传统 APP _{SWE /PS1ΔE9 转基因小鼠不同组织中的线粒体形态。}年轻的Slc25a46敲除小鼠和老年 APP _SWE/PS1ΔE9 小鼠模型在小脑组织中显示出类似的线粒体损伤。结果表明，不同的线粒体相关疾病具有相似的线粒体形态改变和缺陷。此外，黑果枸杞。提取物，一种具有改善认知特性的生物活性食物物质，可以有效地提高Slc25a46 的肌肉力量和增加体重基因敲除小鼠。这些发现表明，小鼠模型中的线粒体形态缺陷，尤其是线粒体区室中的线粒体形态缺陷，代表了一种统一且有效的标记，可用于筛选和验证具有线粒体保护特性的天然产物衍生功能物质。它还在线粒体受损的老年神经退行性疾病，尤其是 AD 中具有潜在的应用价值。