Singh Rajat, Kaushik Susmita, Wang Yongjun, Xiang Youqing, Novak Inna, Komatsu Masaaki, Tanaka Keiji, Cuervo Ana Maria, Czaja Mark J
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Nature. 2009 Apr 30;458(7242):1131-5. doi: 10.1038/nature07976. Epub 2009 Apr 1.
The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.
脂质的细胞内储存和利用对于维持细胞能量稳态至关重要。在营养缺乏期间，以甘油三酯形式储存在脂滴中的细胞脂质会水解为脂肪酸以供能。细胞对饥饿的第二种反应是自噬的诱导，自噬将包裹在双膜囊泡（自噬体）中的细胞内蛋白质和细胞器运送到溶酶体进行降解并用作能量来源。脂解作用和自噬在调节和功能上有相似之处，但尚不清楚它们是否相互关联。在这里，我们展示了自噬在调节细胞内脂质储存（大自噬）方面一个以前未知的功能。在营养缺乏期间，脂滴与自噬成分相关联，并且在培养的肝细胞和小鼠肝脏中抑制自噬会增加脂滴中甘油三酯的储存。这项研究确定了自噬在脂质代谢中的关键功能，这可能对脂质过度积累的人类疾病（如构成代谢综合征的疾病）具有重要意义。
