美国华盛顿大学医学院David J. Pagliarini课题组发现，三酰甘油分解是线粒体应激恢复的基础。该项研究成果发表在2025年1月8日出版的《自然—细胞生物学》上。

据了解，线粒体是无数生化过程发生的关键，因此，如果不加以修复，即使线粒体受到轻微损伤，也会对细胞产生严重后果。

为了探索细胞克服线粒体压力的策略，研究人员对酿酒酵母进行了一系列化学和遗传扰动，并使用深度多组质谱分析法分析了细胞反应。研究发现，调动脂滴中储存的三酰甘油，是菌株成功启动恢复反应的必要条件。

特别是，三酰甘油脂肪酶会分解这些储存的三酰甘油释放酰基链，用于促进线粒体膜脂质心磷脂的生物合成，以支持新的线粒体生物生成。研究证明哺乳动物细胞中也存在类似的修复途径，当缺乏ATGL脂肪酶时，它们无法从多西环素治疗中恢复过来。

总之，该研究揭示了线粒体应激恢复的一个关键组成部分，为进一步探索细胞应对线粒体功能障碍的策略提供了丰富的资源。

附：英文原文

Title: Triacylglycerol mobilization underpins mitochondrial stress recovery

Author: Baker, Zakery N., Zhu, Yunyun, Guerra, Rachel M., Smith, Andrew J., Arra, Aline, Serrano, Lia R., Overmyer, Katherine A., Mukherji, Shankar, Craig, Elizabeth A., Coon, Joshua J., Pagliarini, David J.

Issue&Volume: 2025-01-08

Abstract: Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response. In particular, acyl chains from these stores were liberated by triacylglycerol lipases and used to fuel biosynthesis of the quintessential mitochondrial membrane lipid cardiolipin to support new mitochondrial biogenesis. We demonstrate that a comparable recovery pathway exists in mammalian cells, which fail to recover from doxycycline treatment when lacking the ATGL lipase. Collectively, our work reveals a key component of mitochondrial stress recovery and offers a rich resource for further exploration of the broad cellular responses to mitochondrial dysfunction.

DOI: 10.1038/s41556-024-01586-6

Source: https://www.nature.com/articles/s41556-024-01586-6