依赖二酰甘油酰基转移酶1的脂滴生物合成在饥饿诱导的自噬过程中保护线粒体功能。
DGAT1-Dependent Lipid Droplet Biogenesis Protects Mitochondrial Function during Starvation-Induced Autophagy.
作者信息
Nguyen Truc B, Louie Sharon M, Daniele Joseph R, Tran Quan, Dillin Andrew, Zoncu Roberto, Nomura Daniel K, Olzmann James A
机构信息
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
出版信息
Dev Cell. 2017 Jul 10;42(1):9-21.e5. doi: 10.1016/j.devcel.2017.06.003.
Lipid droplets (LDs) provide an "on-demand" source of fatty acids (FAs) that can be mobilized in response to fluctuations in nutrient abundance. Surprisingly, the amount of LDs increases during prolonged periods of nutrient deprivation. Why cells store FAs in LDs during an energy crisis is unknown. Our data demonstrate that mTORC1-regulated autophagy is necessary and sufficient for starvation-induced LD biogenesis. The ER-resident diacylglycerol acyltransferase 1 (DGAT1) selectively channels autophagy-liberated FAs into new, clustered LDs that are in close proximity to mitochondria and are lipolytically degraded. However, LDs are not required for FA delivery to mitochondria but instead function to prevent acylcarnitine accumulation and lipotoxic dysregulation of mitochondria. Our data support a model in which LDs provide a lipid buffering system that sequesters FAs released during the autophagic degradation of membranous organelles, reducing lipotoxicity. These findings reveal an unrecognized aspect of the cellular adaptive response to starvation, mediated by LDs.
脂滴（LDs）提供了一种“按需”脂肪酸（FAs）来源，可根据营养丰度的波动进行动员。令人惊讶的是，在长期营养剥夺期间，脂滴的数量会增加。在能量危机期间细胞为何将脂肪酸储存于脂滴中尚不清楚。我们的数据表明，mTORC1调节的自噬对于饥饿诱导的脂滴生物合成是必要且充分的。内质网驻留的二酰甘油酰基转移酶1（DGAT1）选择性地将自噬释放的脂肪酸引导至新的、聚集的脂滴中，这些脂滴靠近线粒体并被脂解降解。然而，脂肪酸输送到线粒体并不需要脂滴，相反，脂滴的功能是防止酰基肉碱积累和线粒体的脂毒性失调。我们的数据支持一种模型，即脂滴提供了一个脂质缓冲系统，该系统隔离在膜性细胞器自噬降解过程中释放的脂肪酸，从而降低脂毒性。这些发现揭示了由脂滴介导的细胞对饥饿适应性反应中一个未被认识的方面。
Zotero 插件