Built to last: lysosome remodeling and repair in health and disease
Lysosomes play major roles in growth regulation and catabolism and are recognized as critical mediators of cellular remodeling. An emerging theme is how the lysosome is itself subjected to extensive remodeling in order to perform specific tasks that meet the changing demands of the cell. Accordingly...
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| Published in | Trends in cell biology Vol. 32; no. 7; pp. 597 - 610 |
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| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
01.07.2022
Elsevier BV |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Lysosomes play major roles in growth regulation and catabolism and are recognized as critical mediators of cellular remodeling. An emerging theme is how the lysosome is itself subjected to extensive remodeling in order to perform specific tasks that meet the changing demands of the cell. Accordingly, lysosomes can sustain physical damage and undergo dramatic changes in composition following pathogen infection, accumulation of protein aggregates, or cellular transformation, necessitating dedicated pathways for their repair, remodeling, and restoration. In this review, we focus on emerging molecular mechanisms for piecemeal remodeling of lysosomal components and wholesale repair and discuss their implications in physiological and pathogenic challenges such as cancer, neurodegeneration, and pathogen infection.
The lysosome is a catabolic organelle that is the end point of degradative pathways including endocytosis, phagocytosis, and autophagy.Lysosomal damage can result from accumulation of undigested substrates within the lumen, changes in lipid composition of the membrane, loss of pH and/or membrane potential, and outright rupturing of the lysosomal limiting membrane by mechanical or chemical insults.Lysosomes are subject to continuous remodeling and repair via the action of dedicated signaling pathways, which detect lysosomal stress and dysfunction and trigger both transcriptional and post-translational programs that adjust lysosomal function in a compensatory manner.Prompt repair of lysosomal injury is important for numerous cell types and especially essential for neuronal cells, while enhanced biogenesis and plasticity are emerging as key adaptive mechanisms in cancer cells. |
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| AbstractList | Lysosomes play major roles in growth regulation and catabolism and are recognized as critical mediators of cellular remodeling. An emerging theme is how the lysosome is itself subjected to extensive remodeling in order to perform specific tasks that meet the changing demands of the cell. Accordingly, lysosomes can sustain physical damage and undergo dramatic changes in composition following pathogen infection, accumulation of protein aggregates, or cellular transformation, necessitating dedicated pathways for their repair, remodeling, and restoration. In this review, we focus on emerging molecular mechanisms for piecemeal remodeling of lysosomal components and wholesale repair and discuss their implications in physiological and pathogenic challenges such as cancer, neurodegeneration, and pathogen infection. Lysosomes play major roles in growth regulation and catabolism and are recognized as critical mediators of cellular remodeling. An emerging theme is how the lysosome is itself subjected to extensive remodeling in order to perform specific tasks that meet the changing demands of the cell. Accordingly, lysosomes can sustain physical damage and undergo dramatic changes in composition following pathogen infection, accumulation of protein aggregates, or cellular transformation, necessitating dedicated pathways for their repair, remodeling, and restoration. In this review, we focus on emerging molecular mechanisms for piecemeal remodeling of lysosomal components and wholesale repair and discuss their implications in physiological and pathogenic challenges such as cancer, neurodegeneration, and pathogen infection.Lysosomes play major roles in growth regulation and catabolism and are recognized as critical mediators of cellular remodeling. An emerging theme is how the lysosome is itself subjected to extensive remodeling in order to perform specific tasks that meet the changing demands of the cell. Accordingly, lysosomes can sustain physical damage and undergo dramatic changes in composition following pathogen infection, accumulation of protein aggregates, or cellular transformation, necessitating dedicated pathways for their repair, remodeling, and restoration. In this review, we focus on emerging molecular mechanisms for piecemeal remodeling of lysosomal components and wholesale repair and discuss their implications in physiological and pathogenic challenges such as cancer, neurodegeneration, and pathogen infection. Lysosomes play major roles in growth regulation and catabolism and are recognized as critical mediators of cellular remodeling. An emerging theme is how the lysosome is itself subjected to extensive remodeling in order to perform specific tasks that meet the changing demands of the cell. Accordingly, lysosomes can sustain physical damage and undergo dramatic changes in composition following pathogen infection, accumulation of protein aggregates, or cellular transformation, necessitating dedicated pathways for their repair, remodeling, and restoration. In this review, we focus on emerging molecular mechanisms for piecemeal remodeling of lysosomal components and wholesale repair and discuss their implications in physiological and pathogenic challenges such as cancer, neurodegeneration, and pathogen infection. The lysosome is a catabolic organelle that is the end point of degradative pathways including endocytosis, phagocytosis, and autophagy.Lysosomal damage can result from accumulation of undigested substrates within the lumen, changes in lipid composition of the membrane, loss of pH and/or membrane potential, and outright rupturing of the lysosomal limiting membrane by mechanical or chemical insults.Lysosomes are subject to continuous remodeling and repair via the action of dedicated signaling pathways, which detect lysosomal stress and dysfunction and trigger both transcriptional and post-translational programs that adjust lysosomal function in a compensatory manner.Prompt repair of lysosomal injury is important for numerous cell types and especially essential for neuronal cells, while enhanced biogenesis and plasticity are emerging as key adaptive mechanisms in cancer cells. |
| Author | Perera, Rushika M. Zoncu, Roberto |
| AuthorAffiliation | 2 Department of Anatomy, Department of Pathology, and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143 1 Department of Molecular and Cellular Biology, and Innovative Genomics Institute, University of California at Berkeley, Berkeley, CA 94720 |
| AuthorAffiliation_xml | – name: 2 Department of Anatomy, Department of Pathology, and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143 – name: 1 Department of Molecular and Cellular Biology, and Innovative Genomics Institute, University of California at Berkeley, Berkeley, CA 94720 |
| Author_xml | – sequence: 1 givenname: Roberto surname: Zoncu fullname: Zoncu, Roberto email: rzoncu@berkeley.edu organization: Department of Molecular and Cellular Biology, University of California at Berkeley, Berkeley, CA 94720, USA – sequence: 2 givenname: Rushika M. orcidid: 0000-0003-2435-2273 surname: Perera fullname: Perera, Rushika M. email: rushika.perera@ucsf.edu organization: Department of Anatomy, University of California at San Francisco, San Francisco, CA 94143, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35123838$$D View this record in MEDLINE/PubMed |
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7 |
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| SubjectTerms | cancer Catabolism Damage accumulation Humans infection lysosome Lysosomes Lysosomes - metabolism membrane damage Molecular modelling Neoplasms - pathology Neurodegeneration Pathogens Repair |
| Title | Built to last: lysosome remodeling and repair in health and disease |
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