Nature 458, 1131-1135 (30 April 2009) | doi:10.1038/nature07976; Received 9 November 2008; Accepted 12 March 2009; Published online 1 April 2009

Autophagy regulates lipid metabolism

Rajat Singh1,2,7, Susmita Kaushik1,2,3,4,7, Yongjun Wang1,2, Youqing Xiang1,2, Inna Novak2,5, Masaaki Komatsu6, Keiji Tanaka6, Ana Maria Cuervo1,2,3,4 & Mark J. Czaja1,2

  1. Department of Medicine,
  2. The Marion Bessin Liver Research Center,
  3. Department of Developmental and Molecular Biology,
  4. Institute for Aging Studies,
  5. Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
  6. Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan
  7. These authors contributed equally to this work.

Correspondence to: Ana Maria Cuervo1,2,3,4Mark J. Czaja1,2 Correspondence and requests for materials should be addressed to M.J.C. (Email: or A.M.C. (Email:


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.


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