ATG14 facilitated lipophagy in cancer cells induce ER stress mediated mitoptosis through a ROS dependent pathway

Mukhopadhyay, Subhadip; Schlaepfer, Isabel R.; Bergman, Bryan C.; Panda, Prashanta Kumar; Praharaj, Prakash Priyadarshi; Naik, Prajna Paramita; Agarwal, Rajesh; Bhutia, Sujit K.

doi:10.1016/j.freeradbiomed.2017.01.007

Cited by 58 publications

(38 citation statements)

References 39 publications

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“…It has been reported that ATG14induced cytoprotective autophagy is a pivotal factor to mediate the sensitivity of cancer cells to cisplatin-produced apoptosis [40,41]. Mukhopadhyay et al also demonstrated that ATG14 facilitated lipophagy could induce endoplasmic reticulum stress mediated mitoptosis in cancer cells [42]. The crosstalk between autophagy and apoptosis are recognized as key molecular mechanism involved in the tumor progression [43].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Upregulation of lncRNA HAGLROS enhances the development of nasopharyngeal carcinoma via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals

Zhang

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Upregulation of lncRNA HAGLROS enhances the development of nasopharyngeal carcinoma via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals

Zhang

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…In the reverse experiment, providing exogenous PLIN2 is sufficient to restore LDs and to suppress the cell death of ccRCC cells lacking HIF-2α activity [100]. In another cancer context, Hela cells, overexpression of the autophagy protein ATG14 stimulates lipophagy, the selective autophagy of lipid droplets, leading to an increase in free FAs and concomitant ER stress [101]. In all four of the above mammalian contexts, the storage of triglycerides in LDs appears to play a critical role in mitigating ER stress.…”

Section: 2 Roles For Lipid Droplets In Managing Cell Stressmentioning

confidence: 99%

Lipid droplet functions beyond energy storage

Welte

Gould

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

442

358

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Lipid droplets are cytoplasmic organelles that store neutral lipids and are critically important for energy metabolism. Their function in energy storage is firmly established and increasingly well characterized. However, emerging evidence indicates that lipid droplets also play important and diverse roles in the cellular handling of lipids and proteins that may not be directly related to energy homeostasis. Lipid handling roles of droplets include the storage of hydrophobic vitamin and signaling precursors, and the management of endoplasmic reticulum and oxidative stress. Roles of lipid droplets in protein handling encompass functions in the maturation, storage, and turnover of cellular and viral polypeptides. Other potential roles of lipid droplets may be connected with their intracellular motility and, in some cases, their nuclear localization. This diversity highlights that lipid droplets are very adaptable organelles, performing different functions in different biological contexts.

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“…The role of lipophagy in cancer has not been addressed by many studies so far. While several reports have indicated tumour promoting effects of lipophagy [ 261 , 262 ], most studies so far suggest that lipophagy restricts tumourigenesis [ 263 , 264 , 265 , 266 ]. Microtubule-associated protein 1S (MAP1S)-mediated lipophagy promotes lipid droplet clearance and higher levels of MAP1S have been associated with reduced tumour growth and metastasis and an increased patient survival in clear-cell renal cell carcinoma [ 263 ].…”

Section: Lipid Droplets and Autophagy/lipophagymentioning

confidence: 99%

“…Microtubule-associated protein 1S (MAP1S)-mediated lipophagy promotes lipid droplet clearance and higher levels of MAP1S have been associated with reduced tumour growth and metastasis and an increased patient survival in clear-cell renal cell carcinoma [ 263 ]. Another study has shown that overexpression of ATG14 facilitates lipid droplet breakdown in Hela cells and induces free FA accumulation leading to ER stress- and ROS-mediated apoptosis, whereas suppression of lipophagy by 3-methyladenine (3-MA) or inhibition of lysosomal acid lipase (LAL) reverses these effects [ 264 ]. LAL catalyses both TAG and CE hydrolysis in the lysosome and its deficiency or inhibition leads to several pathologies associated with elevated lysosomal lipid accumulation in mice and humans [ 56 ].…”

Section: Lipid Droplets and Autophagy/lipophagymentioning

confidence: 99%

Lipid Droplets in Cancer: Guardians of Fat in a Stressful World

2018

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Cancer cells possess remarkable abilities to adapt to adverse environmental conditions. Their survival during severe nutrient and oxidative stress depends on their capacity to acquire extracellular lipids and the plasticity of their mechanisms for intracellular lipid synthesis, mobilisation, and recycling. Lipid droplets, cytosolic fat storage organelles present in most cells from yeast to men, are emerging as major regulators of lipid metabolism, trafficking, and signalling in various cells and tissues exposed to stress. Their biogenesis is induced by nutrient and oxidative stress and they accumulate in various cancers. Lipid droplets act as switches that coordinate lipid trafficking and consumption for different purposes in the cell, such as energy production, protection against oxidative stress or membrane biogenesis during rapid cell growth. They sequester toxic lipids, such as fatty acids, cholesterol and ceramides, thereby preventing lipotoxic cell damage and engage in a complex relationship with autophagy. Here, we focus on the emerging mechanisms of stress-induced lipid droplet biogenesis; their roles during nutrient, lipotoxic, and oxidative stress; and the relationship between lipid droplets and autophagy. The recently discovered principles of lipid droplet biology can improve our understanding of the mechanisms that govern cancer cell adaptability and resilience to stress.

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ATG14 facilitated lipophagy in cancer cells induce ER stress mediated mitoptosis through a ROS dependent pathway

Cited by 58 publications

References 39 publications

RETRACTED ARTICLE: Upregulation of lncRNA HAGLROS enhances the development of nasopharyngeal carcinoma via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals

RETRACTED ARTICLE: Upregulation of lncRNA HAGLROS enhances the development of nasopharyngeal carcinoma via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals

Lipid droplet functions beyond energy storage

Lipid Droplets in Cancer: Guardians of Fat in a Stressful World

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