Autophagy - how to control your intracellular diet

Tschachler, Erwin; Eckhart, Leopold

doi:10.1111/bjd.15566

Cited by 7 publications

(11 citation statements)

References 17 publications

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“…The autophagosomes subsequently fuse with lysosomes, thereby exposing their contents to degradative enzymes. [1,2] Autophagy was initially described as a nonspecific response mechanism to nutrient deprivation, [5] but is now recognised to also specifically target damaged proteins and subcellular organelles including mitochondria (mitophagy), endoplasmic reticulum (ERphagy), peroxisomes (pexophagy) and lipid droplets (lipophagy) (reviewed in Refs [6][7][8][9][10]).…”

Section: Introductionmentioning

confidence: 99%

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

Rossiter

Stübiger

Gröger

et al. 2018

Experimental Dermatology

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We have reported recently that inactivation of the essential autophagy-related gene 7 (Atg7) in keratinocytes has little or no impact on morphology and function of the epidermal barrier in experimental animals. When these mice aged, mutant males, (Atg7 ΔKC), developed an oily coat. As the keratin 14 promoter driven cre/LoxP system inactivates floxed Atg7 in all keratin 14 (K14) expressing cells, including sebocytes, we investigated whether the oily hair phenotype was the consequence of changes in function of the skin sebaceous glands. Using an antibody to the GFP-LC3 fusion protein, autophagosomes were detected at the border of sebocyte disintegration in control but not in mutant animals, suggesting that autophagy was (a) active in normal sebaceous glands and (b) was inactivated in the mutant mice. Detailed analysis established that dorsal sebaceous glands were about twice as large in all Atg7 ΔKC mice compared to those of controls (Atg7 F/F), and their rate of sebocyte proliferation was increased. In addition, male mutant mice yielded twice as much lipid per unit hair as age-matched controls. Analysis of sebum lipids by thin layer chromatography revealed a 40% reduction in the proportion of free fatty acids (FFA) and cholesterol, and a 5-fold increase in the proportion of fatty acid methyl esters (FAME). In addition, the most common diester wax species (58-60 carbon atoms) were increased, while shorter species (54-55 carbon atoms) were under-represented in mutant sebum. Our data show that autophagy contributes to sebaceous gland function and to the control of sebum composition.

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Section: Introductionmentioning

confidence: 99%

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

Rossiter

Stübiger

Gröger

et al. 2018

Experimental Dermatology

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“…Adaptor proteins such as sequestosome 1, also known as p62 [ 4 ], differentially bind to autophagy substrates and introduce specificity into the degradation process [ 3 ]. Autophagy removes many types of protein aggregates, dysfunctional organelles, and other potentially dangerous cell components but also contributes to the recycling of macromolecules to ensure cellular homeostasis [ 3 , 5 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Cell types of different functions and turnover rates vary in their dependence on autophagy for the elimination of damaged organelles and potentially harmful protein aggregates as well as for recycling of building blocks of macromolecules [ 3 , 8 , 15 ]. While constitutive deletion of either Atg5 or Atg7 leads to perinatal lethality in mice [ 16 , 17 ], cell type-specific deletions of autophagy genes via the Cre-loxP system allows to inactivate autophagy in a targeted manner and to determine whether lack of autophagy plays essential roles in these specific cells [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Filamentous Aggregation of Sequestosome-1/p62 in Brain Neurons and Neuroepithelial Cells upon Tyr-Cre-Mediated Deletion of the Autophagy Gene Atg7

et al. 2018

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Defects in autophagy and the resulting deposition of protein aggregates have been implicated in aging and neurodegenerative diseases. While gene targeting in the mouse has facilitated the characterization of these processes in different types of neurons, potential roles of autophagy and accumulation of protein substrates in neuroepithelial cells have remained elusive. Here we report that Atg7f/f Tyr-Cre mice, in which autophagy-related 7 (Atg7) is conditionally deleted under the control of the tyrosinase promoter, are a model for accumulations of the autophagy adapter and substrate sequestosome-1/p62 in both neuronal and neuroepithelial cells. In the brain of Atg7f/f Tyr-Cre but not of fully autophagy competent control mice, p62 aggregates were present in sporadic neurons in the cortex and other brain regions as well in epithelial cells of the choroid plexus and the ependyma. Western blot analysis confirmed a dramatic increase of p62 abundance and formation of high-molecular weight species of p62 in the brain of Atg7f/f Tyr-Cre mice relative to Atg7f/f controls. Immuno-electron microscopy showed that p62 formed filamentous aggregates in neurons and ependymal cells. p62 aggregates were also highly abundant in the ciliary body in the eye. Atg7f/f Tyr-Cre mice reached an age of more than 2 years although neurological defects manifesting in abnormal hindlimb clasping reflexes were evident in old mice. These results show that p62 filaments form in response to impaired autophagy in vivo and suggest that Atg7f/f Tyr-Cre mice are a model useful to study the long-term effects of autophagy deficiency on the homeostasis of different neuroectoderm-derived cells.Electronic supplementary materialThe online version of this article (10.1007/s12035-018-0996-x) contains supplementary material, which is available to authorized users.

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“…Autophagy is an evolutionarily conserved intracellular degradation process in which cell constituents are enclosed in double-membraned vesicles and transported to lysosomes (Tschachler and Eckhart, 2017). Suppression of autophagy in mice that carry a floxed Atg7 gene and the K14-Cre transgene (Atg7 f/f K14-Cre) to delete Atg7 in keratinocytes, leads to thickening of the epidermis without skin barrier impairment (Rossiter et al, 2013).…”

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confidence: 99%

“…Due to the unique role of sweat glands in thermoregulation and much higher lifetime in humans, the mouse is an insufficient preclinical model of sweat gland biology, and the roles of autophagy and p62 remain to be investigated further in human sweat glands. Given the growing interest in therapeutic strategies aimed at either enhancement or suppression of autophagy (Tschachler and Eckhart, 2017), it will be important to evaluate the effects of autophagy-modulating therapies on skin appendages, including sweat glands, that are particularly dependent on autophagy. Thin sections through footpads of (a, c, e) wild-type (WT, Atg7 f/f ) and (b, d, f) knockout (KO, Atg7 f/f K14-Cre) mice (age: 1 y) were immunolabeled for p62 (red).…”

mentioning

confidence: 99%

Suppression of Epithelial Autophagy Compromises the Homeostasis of Sweat Glands during Aging

Sukseree

Bergmann

Pajdzik

et al. 2018

Journal of Investigative Dermatology

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Autophagy - how to control your intracellular diet

Cited by 7 publications

References 17 publications

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

Filamentous Aggregation of Sequestosome-1/p62 in Brain Neurons and Neuroepithelial Cells upon Tyr-Cre-Mediated Deletion of the Autophagy Gene Atg7

Suppression of Epithelial Autophagy Compromises the Homeostasis of Sweat Glands during Aging

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