Cells

Editorial

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4 pages, 177 KiB

Open AccessEditorial

Advances in Autophagy, Tissue Injury, and Homeostasis: Cells Special Issue

by Pei-Hui Lin

Cells 2019, 8(7), 743; https://doi.org/10.3390/cells8070743 - 19 Jul 2019

Cited by 4 | Viewed by 3195

Abstract

Macroautophagy (hereafter referred to as autophagy, a word derived from Greek meaning “auto-digestion”) is a lysosome-dependent quality control process to degrade and turnover damaged or senescent organelles and proteins for cellular renewal [...] Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

Research

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19 pages, 9267 KiB

Open AccessArticle

Ethanol-Induced Mitochondrial Damage in Sertoli Cells is Associated with Parkin Overexpression and Activation of Mitophagy

by Nabil Eid, Yuko Ito, Akio Horibe, Yoshinori Otsuki and Yoichi Kondo

Cells 2019, 8(3), 283; https://doi.org/10.3390/cells8030283 - 25 Mar 2019

Cited by 20 | Viewed by 6434

Abstract

This study was conducted to elucidate the involvement of the PINK1-Parkin pathway in ethanol-induced mitophagy among Sertoli cells (SCs). In the research, adult rats were given intraperitoneal injections of ethanol (5 gm/kg) and sacrificed at various time periods within 24 h. Transmission electron [...] Read more.

This study was conducted to elucidate the involvement of the PINK1-Parkin pathway in ethanol-induced mitophagy among Sertoli cells (SCs). In the research, adult rats were given intraperitoneal injections of ethanol (5 gm/kg) and sacrificed at various time periods within 24 h. Transmission electron microscopy was applied to reveal enhanced mitochondrial damage in SCs of the ethanol-treated rats (ETRs) in association with a significant increase in numbers of mitophagic vacuoles (mitophagosomes and autolysosomes) in contrast to very low levels in a control group treated with phosphate-buffered saline (PBS). This enhancement was ultra-structurally verified via observation of trapped mitochondria within LC3-labeled membranes, upregulation of LC3 protein levels, colocalization of LC3 and cytochrome c, and reduced expression of mitochondrial proteins. Importantly, Parkin expression was found to be upregulated in ETR SCs, specifically in mitochondria and mitophagosomes in addition to colocalization with PINK1 and pan-cathepsin, indicating augmented mitophagy. Transcription factor EB (TFEB, a transcription factor for autophagy and mitophagy proteins) was also found to be upregulated in nuclei of ETR SCs and associated with enhanced expression of iNOS. Enhanced Parkin-related mitophagy in ETR SCs may be a protective mechanism with therapeutic implications. To the authors’ knowledge, this is the first report demonstrating the ultrastructural characteristics and molecular mechanisms of Parkin-related mitophagy in ETR SCs. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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23 pages, 5968 KiB

Open AccessArticle

Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy

by Ping Zhou, Weijie Xie, Xiangbao Meng, Yadong Zhai, Xi Dong, Xuelian Zhang, Guibo Sun and Xiaobo Sun

Cells 2019, 8(3), 213; https://doi.org/10.3390/cells8030213 - 2 Mar 2019

Cited by 118 | Viewed by 8189 | Correction

Abstract

Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. [...] Read more.

Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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22 pages, 1932 KiB

Open AccessArticle

Metformin Impairs Glutamine Metabolism and Autophagy in Tumour Cells

by Serena Saladini, Michele Aventaggiato, Federica Barreca, Emanuela Morgante, Luigi Sansone, Matteo A. Russo and Marco Tafani

Cells 2019, 8(1), 49; https://doi.org/10.3390/cells8010049 - 14 Jan 2019

Cited by 27 | Viewed by 6287

Abstract

Metformin has been shown to inhibit glutaminase (GLS) activity and ammonia accumulation thereby reducing the risk of hepatic encephalopathy in type 2 diabetic patients. Since tumour cells are addicted to glutamine and often show an overexpression of glutaminase, we hypothesize that the antitumoral [...] Read more.

Metformin has been shown to inhibit glutaminase (GLS) activity and ammonia accumulation thereby reducing the risk of hepatic encephalopathy in type 2 diabetic patients. Since tumour cells are addicted to glutamine and often show an overexpression of glutaminase, we hypothesize that the antitumoral mechanism of metformin could be ascribed to inhibition of GLS and reduction of ammonia and ammonia-induced autophagy. Our results show that, in different tumour cell lines, micromolar doses of metformin prevent cell growth by reducing glutamate, ammonia accumulation, autophagy markers such as MAP1LC3B-II and GABARAP as well as degradation of long-lived proteins. Reduced autophagy is then accompanied by increased BECN1/BCL2 binding and apoptotic cell death. Interestingly, GLS-silenced cells reproduce the effect of metformin treatment showing reduced MAP1LC3B-II and GABARAP as well as ammonia accumulation. Since metformin is used as adjuvant drug to increase the efficacy of cisplatin-based neoadjuvant chemotherapy, we co-treated tumour cells with micromolar doses of metformin in the presence of cisplatin observing a marked reduction of MAP1LC3B-II and an increase of caspase 3 cleavage. In conclusion, our work demonstrates that the anti-tumoral action of metformin is due to the inhibition of glutaminase and autophagy and could be used to improve the efficacy of chemotherapy. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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25 pages, 7885 KiB

Open AccessArticle

Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway

by Nesrine Ebrahim, Inas A. Ahmed, Noha I. Hussien, Arigue A. Dessouky, Ayman Samir Farid, Amal M. Elshazly, Ola Mostafa, Walaa Bayoumie El Gazzar, Safwa M. Sorour, Yasmin Seleem, Ahmed M. Hussein and Dina Sabry

Cells 2018, 7(12), 226; https://doi.org/10.3390/cells7120226 - 22 Nov 2018

Cited by 183 | Viewed by 9993

Abstract

Background: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy [...] Read more.

Background: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA. Conclusion: We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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17 pages, 6729 KiB

Open AccessArticle

Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury

by Nadezda V. Andrianova, Stanislovas S. Jankauskas, Ljubava D. Zorova, Irina B. Pevzner, Vasily A. Popkov, Denis N. Silachev, Egor Y. Plotnikov and Dmitry B. Zorov

Cells 2018, 7(10), 178; https://doi.org/10.3390/cells7100178 - 22 Oct 2018

Cited by 20 | Viewed by 5496

Abstract

Dietary restriction (DR) is one of the most efficient approaches ameliorating the severity of different pathological conditions including aging. We investigated the protective potential of short-term DR in the model of acute kidney injury (AKI) in young and old rats. In kidney tissue, [...] Read more.

Dietary restriction (DR) is one of the most efficient approaches ameliorating the severity of different pathological conditions including aging. We investigated the protective potential of short-term DR in the model of acute kidney injury (AKI) in young and old rats. In kidney tissue, the levels of autophagy and mitophagy were examined, and proliferative properties of renal cells obtained from rats of different age were compared. DR afforded a significant nephroprotection to ischemic kidneys of young rats. However, in old rats, DR did not provide such beneficial effect. On the assessment of the autophagy marker, the LC3 II/LC3 I ratio, and after staining the tissue with LysoTracker Green, we concluded that in old rats activity of the autophagic-lysosomal system decreased. Mitophagy, as assessed by the levels of PINK-1, was also deteriorated in old animals. Renal cells from old rats showed impaired proliferative capacity, a worse rate of recovery after ischemic injury, increased levels of oxidative stress, accumulation of lipofuscin granules and lower mitochondria membrane potential. The results suggest that the loss of DR benefits in old animals could be due to deterioration in the autophagy/mitophagy flux. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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Review

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21 pages, 788 KiB

Open AccessReview

Autophagy in Neurotrauma: Good, Bad, or Dysregulated

by Junfang Wu and Marta M. Lipinski

Cells 2019, 8(7), 693; https://doi.org/10.3390/cells8070693 - 10 Jul 2019

Cited by 93 | Viewed by 6183

Abstract

Autophagy is a physiological process that helps maintain a balance between the manufacture of cellular components and breakdown of damaged organelles and other toxic cellular constituents. Changes in autophagic markers are readily detectable in the spinal cord and brain following neurotrauma, including traumatic [...] Read more.

Autophagy is a physiological process that helps maintain a balance between the manufacture of cellular components and breakdown of damaged organelles and other toxic cellular constituents. Changes in autophagic markers are readily detectable in the spinal cord and brain following neurotrauma, including traumatic spinal cord and brain injury (SCI/TBI). However, the role of autophagy in neurotrauma remains less clear. Whether autophagy is good or bad is under debate, with strong support for both a beneficial and detrimental role for autophagy in experimental models of neurotrauma. Emerging data suggest that autophagic flux, a measure of autophagic degradation activity, is impaired in injured central nervous systems (CNS), and interventions that stimulate autophagic flux may provide neuroprotection in SCI/TBI models. Recent data demonstrating that neurotrauma can cause lysosomal membrane damage resulting in pathological autophagosome accumulation in the spinal cord and brain further supports the idea that the impairment of the autophagy–lysosome pathway may be a part of secondary injury processes of SCI/TBI. Here, we review experimental work on the complex and varied responses of autophagy in terms of both the beneficial and detrimental effects in SCI and TBI models. We also discuss the existing and developing therapeutic options aimed at reducing the disruption of autophagy to protect the CNS after injuries. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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24 pages, 3377 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Recent Data on Cellular Component Turnover: Focus on Adaptations to Physical Exercise

by Anthony MJ Sanchez, Robin Candau and Henri Bernardi

Cells 2019, 8(6), 542; https://doi.org/10.3390/cells8060542 - 5 Jun 2019

Cited by 33 | Viewed by 8667

Abstract

Significant progress has expanded our knowledge of the signaling pathways coordinating muscle protein turnover during various conditions including exercise. In this manuscript, the multiple mechanisms that govern the turnover of cellular components are reviewed, and their overall roles in adaptations to exercise training [...] Read more.

Significant progress has expanded our knowledge of the signaling pathways coordinating muscle protein turnover during various conditions including exercise. In this manuscript, the multiple mechanisms that govern the turnover of cellular components are reviewed, and their overall roles in adaptations to exercise training are discussed. Recent studies have highlighted the central role of the energy sensor (AMP)-activated protein kinase (AMPK), forkhead box class O subfamily protein (FOXO) transcription factors and the kinase mechanistic (or mammalian) target of rapamycin complex (MTOR) in the regulation of autophagy for organelle maintenance during exercise. A new cellular trafficking involving the lysosome was also revealed for full activation of MTOR and protein synthesis during recovery. Other emerging candidates have been found to be relevant in organelle turnover, especially Parkin and the mitochondrial E3 ubiquitin protein ligase (Mul1) pathways for mitochondrial turnover, and the glycerolipids diacylglycerol (DAG) for protein translation and FOXO regulation. Recent experiments with autophagy and mitophagy flux assessment have also provided important insights concerning mitochondrial turnover during ageing and chronic exercise. However, data in humans are often controversial and further investigations are needed to clarify the involvement of autophagy in exercise performed with additional stresses, such as hypoxia, and to understand the influence of exercise modality. Improving our knowledge of these pathways should help develop therapeutic ways to counteract muscle disorders in pathological conditions. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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21 pages, 2033 KiB

Open AccessReview

Autophagy as a Therapeutic Target to Enhance Aged Muscle Regeneration

by David E. Lee, Akshay Bareja, David B. Bartlett and James P. White

Cells 2019, 8(2), 183; https://doi.org/10.3390/cells8020183 - 20 Feb 2019

Cited by 48 | Viewed by 9984

Abstract

Skeletal muscle has remarkable regenerative capacity, relying on precise coordination between resident muscle stem cells (satellite cells) and the immune system. The age-related decline in skeletal muscle regenerative capacity contributes to the onset of sarcopenia, prolonged hospitalization, and loss of autonomy. Although several [...] Read more.

Skeletal muscle has remarkable regenerative capacity, relying on precise coordination between resident muscle stem cells (satellite cells) and the immune system. The age-related decline in skeletal muscle regenerative capacity contributes to the onset of sarcopenia, prolonged hospitalization, and loss of autonomy. Although several age-sensitive pathways have been identified, further investigation is needed to define targets of cellular dysfunction. Autophagy, a process of cellular catabolism, is emerging as a key regulator of muscle regeneration affecting stem cell, immune cell, and myofiber function. Muscle stem cell senescence is associated with a suppression of autophagy during key phases of the regenerative program. Macrophages, a key immune cell involved in muscle repair, also rely on autophagy to aid in tissue repair. This review will focus on the role of autophagy in various aspects of the regenerative program, including adult skeletal muscle stem cells, monocytes/macrophages, and corresponding age-associated dysfunction. Furthermore, we will highlight rejuvenation strategies that alter autophagy to improve muscle regenerative function. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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13 pages, 298 KiB

Open AccessReview

Cardiac Autophagy in Sepsis

by Yuxiao Sun, Ying Cai and Qun S. Zang

Cells 2019, 8(2), 141; https://doi.org/10.3390/cells8020141 - 10 Feb 2019

Cited by 49 | Viewed by 6195

Abstract

Sepsis is a leading cause of death in intensive care units, and cardiac dysfunction is an identified serious component of the multi-organ failure associated with this critical condition. This review summarized the current discoveries and hypotheses of how autophagy changes in the heart [...] Read more.

Sepsis is a leading cause of death in intensive care units, and cardiac dysfunction is an identified serious component of the multi-organ failure associated with this critical condition. This review summarized the current discoveries and hypotheses of how autophagy changes in the heart during sepsis and the underlying mechanisms. Recent investigations suggest that specific activation of autophagy initiation factor Beclin-1 has a potential to protect cardiac mitochondria, attenuate inflammation, and improve cardiac function in sepsis. Accordingly, pharmacological interventions targeting this pathway have a potential to become an effective approach to control sepsis outcomes. The role of autophagy during sepsis pathogenesis has been under intensive investigation in recent years. It is expected that developing therapeutic approaches with specificities targeting at autophagy regulatory factors may provide new opportunities to alleviate organ dysfunction caused by maladaptive autophagy during sepsis. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

19 pages, 1119 KiB

Open AccessReview

Protective Features of Autophagy in Pulmonary Infection and Inflammatory Diseases

by Kui Wang, Yi Chen, Pengju Zhang, Ping Lin, Na Xie and Min Wu

Cells 2019, 8(2), 123; https://doi.org/10.3390/cells8020123 - 3 Feb 2019

Cited by 53 | Viewed by 7533

Abstract

Autophagy is a highly conserved catabolic process involving autolysosomal degradation of cellular components, including protein aggregates, damaged organelles (such as mitochondria, endoplasmic reticulum, and others), as well as various pathogens. Thus, the autophagy pathway represents a major adaptive response for the maintenance of [...] Read more.

Autophagy is a highly conserved catabolic process involving autolysosomal degradation of cellular components, including protein aggregates, damaged organelles (such as mitochondria, endoplasmic reticulum, and others), as well as various pathogens. Thus, the autophagy pathway represents a major adaptive response for the maintenance of cellular and tissue homeostasis in response to numerous cellular stressors. A growing body of evidence suggests that autophagy is closely associated with diverse human diseases. Specifically, acute lung injury (ALI) and inflammatory responses caused by bacterial infection or xenobiotic inhalation (e.g., chlorine and cigarette smoke) have been reported to involve a spectrum of alterations in autophagy phenotypes. The role of autophagy in pulmonary infection and inflammatory diseases could be protective or harmful dependent on the conditions. In this review, we describe recent advances regarding the protective features of autophagy in pulmonary diseases, with a focus on ALI, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), tuberculosis, pulmonary arterial hypertension (PAH) and cystic fibrosis. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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15 pages, 667 KiB

Open AccessReview

Autophagy: Dual Response in the Development of Hepatocellular Carcinoma

by Hamza O. Yazdani, Hai Huang and Allan Tsung

Cells 2019, 8(2), 91; https://doi.org/10.3390/cells8020091 - 28 Jan 2019

Cited by 74 | Viewed by 7169

Abstract

Autophagy is an evolutionary conserved intracellular mechanism which helps eukaryotic cells in maintaining their metabolic state to afford high-efficiency energy requirements. In the physiology of a normal liver and the pathogenesis of liver diseases, autophagy plays a crucial role. Autophagy has been found [...] Read more.

Autophagy is an evolutionary conserved intracellular mechanism which helps eukaryotic cells in maintaining their metabolic state to afford high-efficiency energy requirements. In the physiology of a normal liver and the pathogenesis of liver diseases, autophagy plays a crucial role. Autophagy has been found to be both upregulated and downregulated in different cancers providing the evidence that autophagy plays a dual role in suppressing and promoting cell survival. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the major leading cause of cancer mortality worldwide. In light of its high complexity and poor prognosis, it is essential to improve our understanding of autophagy’s role in HCC. In this review, we summarize the dual mechanism of autophagy in the development of HCC and elucidate the currently used therapeutic strategies for anti-HCC therapy. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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24 pages, 2705 KiB

Open AccessReview

Roles of Autophagy-Related Genes in the Pathogenesis of Inflammatory Bowel Disease

by Sup Kim, Hyuk Soo Eun and Eun-Kyeong Jo

Cells 2019, 8(1), 77; https://doi.org/10.3390/cells8010077 - 21 Jan 2019

Cited by 82 | Viewed by 12638

Abstract

Autophagy is an intracellular catabolic process that is essential for a variety of cellular responses. Due to its role in the maintenance of biological homeostasis in conditions of stress, dysregulation or disruption of autophagy may be linked to human diseases such as inflammatory [...] Read more.

Autophagy is an intracellular catabolic process that is essential for a variety of cellular responses. Due to its role in the maintenance of biological homeostasis in conditions of stress, dysregulation or disruption of autophagy may be linked to human diseases such as inflammatory bowel disease (IBD). IBD is a complicated inflammatory colitis disorder; Crohn’s disease and ulcerative colitis are the principal types. Genetic studies have shown the clinical relevance of several autophagy-related genes (ATGs) in the pathogenesis of IBD. Additionally, recent studies using conditional knockout mice have led to a comprehensive understanding of ATGs that affect intestinal inflammation, Paneth cell abnormality and enteric pathogenic infection during colitis. In this review, we discuss the various ATGs involved in macroautophagy and selective autophagy, including ATG16L1, IRGM, LRRK2, ATG7, p62, optineurin and TFEB in the maintenance of intestinal homeostasis. Although advances have been made regarding the involvement of ATGs in maintaining intestinal homeostasis, determining the precise contribution of autophagy has remained elusive. Recent efforts based on direct targeting of ATGs and autophagy will further facilitate the development of new therapeutic opportunities for IBD. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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20 pages, 2410 KiB

Open AccessReview

Autophagy in Chronic Kidney Diseases

by Tien-An Lin, Victor Chien-Chia Wu and Chao-Yung Wang

Cells 2019, 8(1), 61; https://doi.org/10.3390/cells8010061 - 16 Jan 2019

Cited by 125 | Viewed by 12879

Abstract

Autophagy is a cellular recycling process involving self-degradation and reconstruction of damaged organelles and proteins. Current evidence suggests that autophagy is critical in kidney physiology and homeostasis. In clinical studies, autophagy activations and inhibitions are linked to acute kidney injuries, chronic kidney diseases, [...] Read more.

Autophagy is a cellular recycling process involving self-degradation and reconstruction of damaged organelles and proteins. Current evidence suggests that autophagy is critical in kidney physiology and homeostasis. In clinical studies, autophagy activations and inhibitions are linked to acute kidney injuries, chronic kidney diseases, diabetic nephropathies, and polycystic kidney diseases. Oxidative stress, inflammation, and mitochondrial dysfunction, which are implicated as important mechanisms underlying many kidney diseases, modulate the autophagy activation and inhibition and lead to cellular recycling dysfunction. Abnormal autophagy function can induce loss of podocytes, damage proximal tubular cells, and glomerulosclerosis. After acute kidney injuries, activated autophagy protects tubular cells from apoptosis and enhances cellular regeneration. Patients with chronic kidney diseases have impaired autophagy that cannot be reversed by hemodialysis. Multiple nephrotoxic medications also alter the autophagy signaling, by which the mechanistic insights of the drugs are revealed, thus providing the unique opportunity to manage the nephrotoxicity of these drugs. In this review, we summarize the current concepts of autophagy and its molecular aspects in different kidney cells pathophysiology. We also discuss the current evidence of autophagy in acute kidney injury, chronic kidney disease, toxic effects of drugs, and aging kidneys. In addition, we examine therapeutic possibilities targeting the autophagy system in kidney diseases. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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13 pages, 1013 KiB

Open AccessFeature PaperReview

Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease

by Ralf Weiskirchen and Frank Tacke

Cells 2019, 8(1), 16; https://doi.org/10.3390/cells8010016 - 1 Jan 2019

Cited by 64 | Viewed by 10988

Abstract

Autophagy is a highly conserved intracellular process for the ordered degradation and recycling of cellular components in lysosomes. In the liver, parenchymal cells (i.e., mainly hepatocytes) utilize autophagy to provide amino acids, glucose, and free fatty acids as sources of energy and biosynthesis [...] Read more.

Autophagy is a highly conserved intracellular process for the ordered degradation and recycling of cellular components in lysosomes. In the liver, parenchymal cells (i.e., mainly hepatocytes) utilize autophagy to provide amino acids, glucose, and free fatty acids as sources of energy and biosynthesis functions, but also for recycling and controlling organelles such as mitochondria. Non-parenchymal cells of the liver, including endothelial cells, macrophages (Kupffer cells), and hepatic stellate cells (HSC), also employ autophagy, either for maintaining cellular homeostasis (macrophages, endothelium) or for providing energy for their activation (stellate cells). In hepatocytes, autophagy contributes to essential homeostatic functions (e.g., gluconeogenesis, glycogenolysis, fatty acid oxidation), but is also implicated in diseases. For instance, storage disorders (alpha 1 antitrypsin deficiency, Wilson’s disease), metabolic (non-alcoholic steatohepatitis, NASH), and toxic (alcohol) liver diseases may benefit from augmenting autophagy in hepatocytes. In hepatic fibrosis, autophagy has been implicated in the fibrogenic activation of HSC to collagen-producing myofibroblasts. In hepatocellular carcinoma (HCC), autophagy may contribute to tumor surveillance as well as invasiveness, indicating a dual and stage-dependent function in cancer. As many drugs directly or indirectly modulate autophagy, it is intriguing to investigate autophagy-targeting, possibly even cell type-directed strategies for the treatment of hereditary liver diseases, NASH, fibrosis, and HCC. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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18 pages, 1881 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Impact of Autophagy of Innate Immune Cells on Inflammatory Bowel Disease

by Tomoya Iida, Yoshihiro Yokoyama, Kohei Wagatsuma, Daisuke Hirayama and Hiroshi Nakase

Cells 2019, 8(1), 7; https://doi.org/10.3390/cells8010007 - 22 Dec 2018

Cited by 30 | Viewed by 7202

Abstract

Autophagy, an intracellular degradation mechanism, has many immunological functions and is a constitutive process necessary for maintaining cellular homeostasis and organ structure. One of the functions of autophagy is to control the innate immune response. Many studies conducted in recent years have revealed [...] Read more.

Autophagy, an intracellular degradation mechanism, has many immunological functions and is a constitutive process necessary for maintaining cellular homeostasis and organ structure. One of the functions of autophagy is to control the innate immune response. Many studies conducted in recent years have revealed the contribution of autophagy to the innate immune response, and relationships between this process and various diseases have been reported. Inflammatory bowel disease is an intractable disorder with unknown etiology; however, immunological abnormalities in the intestines are known to be involved in the pathology of inflammatory bowel disease, as is dysfunction of autophagy. In Crohn’s disease, many associations with autophagy-related genes, such as ATG16L1, IRGM, NOD2, and others, have been reported. Abnormalities in the ATG16L1 gene, in particular, have been reported to cause autophagic dysfunction, resulting in enhanced production of inflammatory cytokines by macrophages as well as abnormal function of Paneth cells, which are important in intestinal innate immunity. In this review, we provide an overview of the autophagy mechanism in innate immune cells in inflammatory bowel disease. Full article

(This article belongs to the Special Issue Autophagy in Tissue Injury and Homeostasis)

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