The return of the nucleus: transcriptional and epigenetic control of autophagy

Füllgrabe, Jens; Klionsky, Daniel J.; Joseph, Bertrand

doi:10.1038/nrm3716

Cited by 403 publications

(402 citation statements)

References 145 publications

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“…Recent studies have implicated the transcription factor FoxO1 in autophagy regulation. [22][23][24][25] However, FoxO1 functions in a tissue-dependent way, and a role of FoxO1 in adipose autophagy has not been reported. [20][21][22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

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FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes

et al. 2016

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Obesity and related metabolic disorders constitute one of the most pressing heath concerns worldwide. Increased adiposity is linked to autophagy upregulation in adipose tissues. However, it is unknown how autophagy is upregulated and contributes to aberrant adiposity. Here we show a FoxO1-autophagy-FSP27 axis that regulates adipogenesis and lipid droplet (LD) growth in adipocytes. Adipocyte differentiation was associated with upregulation of autophagy and fat specific protein 27 (FSP27), a key regulator of adipocyte maturation and expansion by promoting LD formation and growth. However, FoxO1 specific inhibitor AS1842856 potently suppressed autophagy, FSP27 expression, and adipocyte differentiation. In terminally differentiated adipocytes, AS1842856 significantly reduced FSP27 level and LD size, which was recapitulated by autophagy inhibitors (bafilomycin-A1 and leupeptin, BL). Similarly, AS1842856 and BL dampened autophagy activity and FSP27 expression in explant cultures of white adipose tissue. To our knowledge, this is the first study addressing FoxO1 in the regulation of adipose autophagy, shedding light on the mechanism of increased autophagy and adiposity in obese individuals. Given that adipogenesis and adipocyte expansion contribute to aberrant adiposity, targeting the FoxO1-autophagy-FSP27 axis may lead to new anti-obesity options.

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Section: Introductionmentioning

confidence: 99%

“…[22][23][24][25] However, FoxO1 functions in a tissue-dependent way, and a role of FoxO1 in adipose autophagy has not been reported. [20][21][22][23][24] . In this study we found that FoxO1 specific antagonist (AS1842856) 3,25 potently suppressed autophagy and adipocyte differentiation, which was associated with downregulation of FSP27.…”

Section: Introductionmentioning

confidence: 99%

FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes

et al. 2016

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“…In fact, for a long time autophagy has been viewed as mainly a cytoplasmic process, especially because enucleated cells are still capable of undergoing autophagy [5]. Recently it is becoming apparent that transcriptional and epigenetic events are also involved in regulating autophagy [6]. One of the first transcription factors identified to be involved in autophagy regulation under amino acid and serum starvation is TFEB (transcription factor EB).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

et al. 2018

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Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation.

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“…Given this potential for harming the cell, and the importance of autophagy in homeostasis and response to stress, the cell utilizes a range of mechanisms to regulate this process at different steps and to ensure that it is finely tuned. In addition to the cytoplasmic post-translational modification of various ATG proteins, recent studies have delved into the transcriptional and epigenetic control of autophagy (3). Notably in human cells, TFEB (transcription factor EB) and ZKSCAN3 (zinc finger with KRAB and SCAN domains 3) have been implicated in playing a central role in autophagy regulation (4,5).…”

mentioning

confidence: 99%

The return of the nucleus: transcriptional and epigenetic control of autophagy

Cited by 403 publications

References 145 publications

FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes

FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

The AMPK-SKP2-CARM1 axis links nutrient sensing to transcriptional and epigenetic regulation of autophagy

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