Autophagy: A Lysosome-Dependent Process with Implications in Cellular Redox Homeostasis and Human Disease.

Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 100888899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7716 (Electronic) Linking ISSN: 15230864 NLM ISO Abbreviation: Antioxid Redox Signal Subsets: MEDLINE

Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., 1999-

Autophagy* ; Homeostasis*; Lysosomes/*metabolism; Animals ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Heart Diseases/metabolism ; Heart Diseases/pathology ; Humans ; Kidney Diseases/metabolism ; Kidney Diseases/pathology ; Liver Diseases/metabolism ; Liver Diseases/pathology ; Lung Diseases/metabolism ; Lung Diseases/pathology ; Metabolic Diseases/metabolism ; Metabolic Diseases/pathology ; Oxidation-Reduction

Significance: Autophagy, a lysosome-dependent homeostatic process inherent to cells and tissues, has emerging significance in the pathogenesis of human disease. This process enables the degradation and turnover of cytoplasmic substrates via membrane-dependent sequestration in autophagic vesicles (autophagosomes) and subsequent lysosomal delivery of cargo. Recent Advances: Selective forms of autophagy can target specific substrates (e.g., organelles, protein aggregates, and lipids) for processing. Autophagy is highly regulated by oxidative stress, including exposure to altered oxygen tension, by direct and indirect mechanisms, and contributes to inducible defenses against oxidative stress. Mitochondrial autophagy (mitophagy) plays a critical role in the oxidative stress response, through maintenance of mitochondrial integrity.
Critical Issues: Autophagy can impact a number of vital cellular processes including inflammation and adaptive immunity, host defense, lipid metabolism and storage, mitochondrial homeostasis, and clearance of aggregated proteins, all which may be of significance in human disease. Autophagy can exert both maladaptive and adaptive roles in disease pathogenesis, which may also be influenced by autophagy impairment. This review highlights the essential roles of autophagy in human diseases, with a focus on diseases in which oxidative stress or inflammation play key roles, including human lung, liver, kidney and heart diseases, metabolic diseases, and diseases of the cardiovascular and neural systems.
Future Directions: Investigations that further elucidate the complex role of autophagy in the pathogenesis of disease will facilitate targeting this pathway for therapies in specific diseases.

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R01 DK057661 United States DK NIDDK NIH HHS; R01 HL060234 United States HL NHLBI NIH HHS; R01 HL079904 United States HL NHLBI NIH HHS; R01 HL133801 United States HL NHLBI NIH HHS

Keywords: autophagy; lysosome; mitophagy; oxidative stress; selective autophagy

Date Created: 20180222 Date Completed: 20200326 Latest Revision: 20231004

20231215

PMC6251060

10.1089/ars.2018.7518

29463101