6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Autophagy and Autophagy-Related Diseases: A Review

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.

          Related collections

          Most cited references157

          • Record: found
          • Abstract: found
          • Article: not found

          mTOR Signaling in Growth, Metabolism, and Disease.

          The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.

            Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Autophagy: renovation of cells and tissues.

              Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. Copyright © 2011 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                26 November 2020
                December 2020
                : 21
                : 23
                : 8974
                Affiliations
                [1 ]Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan; aizenblue138@ 123456gmail.com (T.I.); awakamay.dem1@ 123456gmail.com (T.Y.); a08m081@ 123456gmail.com (T.H.); yoshi_yokoyamaa@ 123456yahoo.co.jp (Y.Y.); polestar100100@ 123456gmail.com (Y.H.); hirarin95@ 123456yahoo.co.jp (D.H.); waga_a05m@ 123456yahoo.co.jp (K.W.)
                [2 ]Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo 160-0023, Japan; itoitakao@ 123456gmail.com
                Author notes
                [* ]Correspondence: hiropynakase@ 123456gmail.com ; Tel.: +81-11-611-2111
                Author information
                https://orcid.org/0000-0003-2434-1048
                https://orcid.org/0000-0002-9842-4850
                https://orcid.org/0000-0002-6774-7868
                https://orcid.org/0000-0003-2848-6586
                Article
                ijms-21-08974
                10.3390/ijms21238974
                7729615
                33255983
                284c9dd2-3c3d-462b-89f7-1cba941cd17b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 September 2020
                : 24 November 2020
                Categories
                Review

                Molecular biology
                autophagy,autophagy-related gene,mitophagy,cancer,neurodegenerative disease,cardiovascular,liver disease

                Comments

                Comment on this article