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Selective Autophagy, Master Regulation of Cells, and Organismal Homeostasis: The Latest Advances and Perspectives

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 15701

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Special Issue Editor

Prof. Dr. Dong-Hyung Cho

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Guest Editor

School of Life Sciences, Graduate School, Kyungpook National University, Daegu 41566, Korea
Interests: autophagy; peroxisome; lysosome; primary cilia; cell death
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Macroautophagy (autophagy) is an essential cellular homeostasis process that degrades cellular contents in response to various cellular and environmental stresses. This catabolic process serves to degrade cytoplasmic contents ranging from abnormal proteins to damaged organelles via the lysosomal system. Since autophagy is an evolutionarily conserved fundamental homeostasis program, dysfunction or dysregulation of autophagy is closely linked to a wide range of human diseases, including neurodegeneration, muscle diseases, cancer, infection, immunological disorders, metabolic diseases, and aging.

In addition to non-selective bulk degradation, recent work has indicated that autophagy targets cargo through selective degradation called selective autophagy (. This capability makes selective autophagy a major process in maintaining cellular homeostasis under specific pathological conditions.

We encourage you to contribute to this Special Issue of ‘Cells’ and submit research articles, review articles, and perspective and opinion articles that are dedicated to autophagy and selective autophagy.

Dr. Dong-Hyung Cho
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

autophagy
homeostasis
selective autophagy
mitophagy
reticulophagy
pexophagy
lysophagy
xenophagy
nucleophayg
ribophagy
lipophagy
melanophagy
aggrephagy
autophagosome
autolysosome
lysosome
organelles
cell signaling
human disease
aging

Published Papers (6 papers)

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Research

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12 pages, 2398 KiB

Open AccessArticle

Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells

by Ha Jung Lee, Seong Hyun Kim, Yong Hwan Kim, So Hyun Kim, Gyeong Seok Oh, Ji-Eun Bae, Joon Bum Kim, Na Yeon Park, Kyuhee Park, Eunbyul Yeom, Kwiwan Jeong, Pansoo Kim, Doo Sin Jo and Dong-Hyung Cho

Cells 2023, 12(1), 146; https://doi.org/10.3390/cells12010146 - 29 Dec 2022

Cited by 3 | Viewed by 1853

Abstract

Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the biogenesis, storage, and transport of melanin in melanocytes. However, the mechanisms underlying melanosomal autophagy, known as the melanophagy pathway, are poorly understood. To better understand the mechanism of melanophagy, we screened an endocrine-hormone chemical library and identified nalfurafine hydrochlorides, a κ-opioid receptor agonist, as a potent inducer of melanophagy. Treatment with nalfurafine hydrochloride increased autophagy and reduced melanin content in alpha-melanocyte-stimulating hormone (α-MSH)-treated cells. Furthermore, inhibition of autophagy blocked melanosomal degradation and reversed the nalfurafine hydrochloride-induced decrease in melanin content in α-MSH-treated cells. Consistently, treatment with other κ-opioid receptor agonists, such as MCOPPB or mianserin, inhibited excessive melanin production but induced autophagy in B16F1 cells. Furthermore, nalfurafine hydrochloride inhibited protein kinase A (PKA) activation, which was notably restored by forskolin, a PKA activator. Additionally, forskolin treatment further suppressed melanosomal degradation as well as the anti-pigmentation activity of nalfurafine hydrochloride in α-MSH-treated cells. Collectively, our data suggest that stimulation of κ-opioid receptors induces melanophagy by inhibiting PKA activation in α-MSH-treated B16F1 cells. Full article

(This article belongs to the Special Issue Selective Autophagy, Master Regulation of Cells, and Organismal Homeostasis: The Latest Advances and Perspectives)

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10 pages, 1780 KiB

Open AccessArticle

Inhibition of BRD4 Promotes Pexophagy by Increasing ROS and ATM Activation

by Yong Hwan Kim, Doo Sin Jo, Na Yeon Park, Ji-Eun Bae, Joon Bum Kim, Ha Jung Lee, So Hyun Kim, Seong Hyun Kim, Sunwoo Lee, Mikyung Son, Kyuhee Park, Kwiwan Jeong, Eunbyul Yeom and Dong-Hyung Cho

Cells 2022, 11(18), 2839; https://doi.org/10.3390/cells11182839 - 12 Sep 2022

Cited by 3 | Viewed by 2300

Abstract

Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely unknown. In this study, we identified several BRD4 inhibitors, including molibresib, a novel pexophagy inducer, via chemical library screening. Treatment with molibresib promotes loss of peroxisomes selectively, but not mitochondria, ER, or Golgi apparatus in HeLa cells. Consistently, depletion of BRD4 expression also induced pexophagy in RPE cells. In addition, the inhibition of BRD4 by molibresib increased autophagic degradation of peroxisome ATG7-dependency. We further found that molibresib produced reactive oxygen species (ROS), which potentiates ATM activation. Inhibition of ROS or ATM suppressed the loss of peroxisomes in molibresib-treated cells. Taken together, our data suggest that inhibition of BRD4 promotes pexophagy by increasing ROS and ATM activation. Full article

(This article belongs to the Special Issue Selective Autophagy, Master Regulation of Cells, and Organismal Homeostasis: The Latest Advances and Perspectives)

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20 pages, 6726 KiB

Open AccessArticle

Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells

by Mooud Amirkavei, Flavia Plastino, Anders Kvanta, Kai Kaarniranta, Helder André and Ari Koskelainen

Cells 2022, 11(11), 1778; https://doi.org/10.3390/cells11111778 - 28 May 2022

Cited by 4 | Viewed by 2348

Abstract

To maintain homeostasis, cells have evolved stress-response pathways to cope with exogenous and endogenous stress factors. Diverse stresses at high doses may be detrimental, albeit low doses of stress, known as hormesis, can be beneficial. Upon exposure to stress, such as temperature rise, the conventional heat shock response (HSR) regulated by the heat shock transcription factor 1 (HSF1) facilitates refolding of misfolded proteins with the help of heat shock proteins (HSPs). However, the role and molecular mechanisms underlying the beneficial effects of HSR with other clearance processes, such as autophagy, remain poorly understood. In this study, human ARPE-19 cells, an in vitro model of retinal pigment epithelium, were treated with hormetic heat shock (HHS) and the autophagy expression profile was examined using quantitative PCR (qPCR), immunoblotting, immunoprecipitation, and immunofluorescence. We demonstrate that HHS enhances the expression of fundamental autophagy-associated genes in ARPE-19 cells through the activation of HSF1. HHS transiently increases the level of SQSTM1 and LC3B-II and activates autophagy. These findings reveal a role for autophagic HSF1-regulated functions and demonstrate the contribution of autophagy to hormesis in the HSR by improving proteostasis. Full article

(This article belongs to the Special Issue Selective Autophagy, Master Regulation of Cells, and Organismal Homeostasis: The Latest Advances and Perspectives)

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Graphical abstract

15 pages, 16838 KiB

Open AccessArticle

Basal Autophagy Is Necessary for A Pharmacologic PPARα Transactivation

by Eun Young Kim and Jae Man Lee

Cells 2022, 11(4), 754; https://doi.org/10.3390/cells11040754 - 21 Feb 2022

Cited by 1 | Viewed by 2100

Abstract

Autophagy is a conserved cellular process of catabolism leading to nutrient recycling upon starvation and maintaining tissue and energy homeostasis. Tissue-specific loss of core-autophagy-related genes often triggers diverse diseases, including cancer, neurodegeneration, inflammatory disease, metabolic disorder, and muscle disease. The nutrient-sensing nuclear receptors peroxisome proliferator-activated receptor α (PPARα) plays a key role in fasting-associated metabolisms such as autophagy, fatty acid oxidation, and ketogenesis. Here we show that autophagy defects impede the transactivation of PPARα. Liver-specific ablation of the Atg7 gene in mice showed reduced expression levels of PPARα target genes in response to its synthetic agonist ligands. Since NRF2, an antioxidant transcription factor, is activated in autophagy-deficient mice due to p62/SQSTM1 accumulation and its subsequent interaction with KEAP1, an E3 ubiquitin ligase. We hypothesize that the nuclear accumulation of NRF2 by autophagy defects blunts the transactivation of PPARα. Consistent with this idea, we find that NRF2 activation is sufficient to inhibit the pharmacologic transactivation of PPARα, which is dependent on the Nrf2 gene. These results reveal an unrecognized requirement of basal autophagy for the transactivation of PPARα by preventing NRF2 from a nuclear translocation and suggest a clinical significance of basal autophagy to expect a pharmacologic efficacy of synthetic PPARα ligands. Full article

(This article belongs to the Special Issue Selective Autophagy, Master Regulation of Cells, and Organismal Homeostasis: The Latest Advances and Perspectives)

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Review

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11 pages, 1353 KiB

Open AccessReview

Post-Translational Modifications of ATG4B in the Regulation of Autophagy

by Na Yeon Park, Doo Sin Jo and Dong-Hyung Cho

Cells 2022, 11(8), 1330; https://doi.org/10.3390/cells11081330 - 13 Apr 2022

Cited by 13 | Viewed by 3311

Abstract

Autophagy plays a key role in eliminating and recycling cellular components in response to stress, including starvation. Dysregulation of autophagy is observed in various diseases, including neurodegenerative diseases, cancer, and diabetes. Autophagy is tightly regulated by autophagy-related (ATG) proteins. Autophagy-related 4 (ATG4) is the sole cysteine protease, and four homologs (ATG4A–D) have been identified in mammals. These proteins have two domains: catalytic and short fingers. ATG4 facilitates autophagy by promoting autophagosome maturation through reversible lipidation and delipidation of seven autophagy-related 8 (ATG8) homologs, including microtubule-associated protein 1-light chain 3 (LC3) and GABA type A receptor-associated protein (GABARAP). Each ATG4 homolog shows a preference for a specific ATG8 homolog. Post-translational modifications of ATG4, including phosphorylation/dephosphorylation, O-GlcNAcylation, oxidation, S-nitrosylation, ubiquitination, and proteolytic cleavage, regulate its activity and ATG8 processing, thus modulating its autophagic activity. We reviewed recent advances in our understanding of the effect of post-translational modification on the regulation, activity, and function of ATG4, the main protease that controls autophagy. Full article

(This article belongs to the Special Issue Selective Autophagy, Master Regulation of Cells, and Organismal Homeostasis: The Latest Advances and Perspectives)

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25 pages, 1609 KiB

Open AccessFeature PaperReview

Transcriptional Regulation of Hepatic Autophagy by Nuclear Receptors

by Eun Young Kim and Jae Man Lee

Cells 2022, 11(4), 620; https://doi.org/10.3390/cells11040620 - 10 Feb 2022

Cited by 10 | Viewed by 2905

Abstract

Autophagy is an adaptive self-eating process involved in degradation of various cellular components such as carbohydrates, lipids, proteins, and organelles. Its activity plays an essential role in tissue homeostasis and systemic metabolism in response to diverse challenges, including nutrient depletion, pathogen invasion, and accumulations of toxic materials. Therefore, autophagy dysfunctions are intimately associated with many human diseases such as cancer, neurodegeneration, obesity, diabetes, infection, and aging. Although its acute post-translational regulation is well described, recent studies have also shown that autophagy can be controlled at the transcriptional and post-transcriptional levels. Nuclear receptors (NRs) are in general ligand-dependent transcription factors consisting of 48 members in humans. These receptors extensively control transcription of a variety of genes involved in development, metabolism, and inflammation. In this review, we discuss the roles and mechanisms of NRs in an aspect of transcriptional regulation of hepatic autophagy, and how the NR-driven autophagy pathway can be harnessed to treat various liver diseases. Full article

(This article belongs to the Special Issue Selective Autophagy, Master Regulation of Cells, and Organismal Homeostasis: The Latest Advances and Perspectives)

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