Selective Autophagy Regulates Lipid Metabolism

Identification: Komatsu, Masaaki


Selective Autophagy Regulates Lipid Metabolism
Masaaki Komatsu
School of Medicine Niigata University, Japan
Past one decade, a growing body of evidence shed light on the importance of selective autophagy in removal of soluble proteins, proteins aggregates, damaged mitochondria, and invasive bacteria. Actually, dysfunctions of selective autophagy have been directly linked to human pathogenic conditions such as metabolic disorders, neurodegenerative diseases and cancer. However, the metabolic regulations through selective autophagy are still largely unknown. Here, we show that a deficiency in selective autophagy is associated with suppression of lipid oxidation via a transcriptional regulatory mechanism. The production of acetyl CoA and ketone bodies upon fasting was significantly impaired by loss of Atg7, which arose from transcriptional down-regulation of genes that encode enzymes involved in β-oxidation. Such down-regulation occurred due to suppression of transactivation of PPARα, a master regulator of lipid metabolism. Mechanistically, NCoR1, a nuclear receptor co-repressor 1, which interacts with PPARα and suppresses its transactivation, bound to GABARAP in a LIR-dependent manner and was degraded by autophagy. Thus, deletion of Atg7 caused marked accumulation of NCoR1 and subsequently suppressed PPARα-activity. These results demonstrate that loss of autophagy causes altered lipid metabolism through selective autophagy, possibly predisposing the organism to develop metabolic diseases.


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