Autophagy—a key player in cellular and body metabolism

Kim, Kook Hwan; Lee, Myung-Shik

doi:10.1038/nrendo.2014.35

Cited by 772 publications

(561 citation statements)

References 189 publications

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“…Autophagy means self-eating in Greek and can function as an intracellular recycling system by which intracellular contents and damaged organelles undergo degradation through their sequestration within autophagosomes and lysosomal degradation to supply energy substrates. [145][146][147][148][149][150][151][152][153] mTORC1 is a critical negative regulator of autophagy. 40,59,154 mTORC1 phosphorylates and inhibits the autophagy-activating kinase ULK1.…”

Section: Hk-ii-mediated Regulation Of Mtorc1 and Autophagymentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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Accumulating evidence reveals that metabolic and cell survival pathways are closely related, sharing common signaling molecules. Hexokinase catalyzes the phosphorylation of glucose, the rate-limiting first step of glycolysis. Hexokinase II (HK-II) is a predominant isoform in insulin-sensitive tissues such as heart, skeletal muscle, and adipose tissues. It is also upregulated in many types of tumors associated with enhanced aerobic glycolysis in tumor cells, the Warburg effect. In addition to the fundamental role in glycolysis, HK-II is increasingly recognized as a component of a survival signaling nexus. This review summarizes recent advances in understanding the protective role of HK-II, controlling cellular growth, preventing mitochondrial death pathway and enhancing autophagy, with a particular focus on the interaction between HK-II and Akt/mTOR pathway to integrate metabolic status with the control of cell survival.

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Section: Hk-ii-mediated Regulation Of Mtorc1 and Autophagymentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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“…The western diet that has been incriminated as a cause of pandemics of metabolic syndrome is also a risk factor for IBD. 23 Since lipid is a target of autophagy and in turn affects autophagy, 1,5 lipid excess in conjunction with autophagy dysfunction due to aging or genetic predisposition could be a common cause of metabolic syndrome and colitis, and autophagy modulators may have a therapeutic potential against these diseases.…”

Section: Figure 7 Systemic Inflammation and Bacterial Invasion Aftermentioning

confidence: 99%

“…1 Since ER (endoplasmic reticulum) and mitochondria that critically affect b-cell function, insulin release and insulin sensitivity depend on autophagy for proper function, 2-4 autophagy of several metabolic organs or systemic autophagy affects nutrient metabolism. 5,6 Furthermore, disturbance of local or systemic autophagy appears to plays a role in dysregulated metabolism and in the development of metabolic syndrome or T2D (type 2 diabetes).…”

Section: Introductionmentioning

confidence: 99%

Autophagy deficiency in myeloid cells increases susceptibility to obesity-induced diabetes and experimental colitis

et al. 2016

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(2016) Autophagy deficiency in myeloid cells increases susceptibility to obesity-induced diabetes and experimental colitis, Autophagy, 12:8, 1390-1403, DOI: 10.1080/15548627.2016 ABSTRACT Autophagy, which is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria, affects diverse aspects of metabolism, and its dysregulation has been incriminated in various metabolic disorders. However, the role of autophagy of myeloid cells in adipose tissue inflammation and type 2 diabetes has not been addressed. We produced mice with myeloid cell-specific deletion of Atg7 (autophagy-related 7), an essential autophagy gene (Atg7 conditional knockout [cKO] mice). While Atg7 cKO mice were metabolically indistinguishable from control mice, they developed diabetes when bred to ob/w mice (Atg7 cKO-ob/ob mice), accompanied by increases in the crown-like structure, inflammatory cytokine expression and inflammasome activation in adipose tissue. Mfs (macrophages) from Atg7 cKO mice showed significantly higher interleukin 1 b release and inflammasome activation in response to a palmitic acid plus lipopolysaccharide combination. Moreover, a decrease in the NAD C :NADH ratio and increase in intracellular ROS content after treatment with palmitic acid in combination with lipopolysaccharide were more pronounced in Mfs from Atg7 cKO mice, suggesting that mitochondrial dysfunction in autophagy-deficient Mfs leads to an increase in lipid-induced inflammasome and metabolic deterioration in Atg7 cKO-ob/ob mice. Atg7 cKO mice were more susceptible to experimental colitis, accompanied by increased colonic cytokine expression, T helper 1 skewing and systemic bacterial invasion. These results suggest that autophagy of Mfs is important for the control of inflammasome activation in response to metabolic or extrinsic stress, and autophagy deficiency in Mfs may contribute to the progression of metabolic syndrome associated with lipid injury and colitis.

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“…The active ULK complex phosphorylates BECN1, a key component of the class III phosphatidylinositol 3-kinase complexes (one of which includes PIK3C3, PIK3R4, BECN1 and ATG14), to promote autophagy. [59][60][61] Upstream of MTORC1, the TSC1-TSC2 complex and the AMPK protein coordinate growth factor and energy signaling cascades. 62,63 In a parallel mechanism, MTORC1 also inhibits autophagy through the phosphorylation and the cytosolic retention of the transcriptional factor TFEB, which controls the expression of genes involved in the execution of autophagy.…”

Section: Regulation and Role Of Autophagy In Cancer Cellsmentioning

confidence: 99%