Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
Cholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. Cholesterol traffics to different cellular compartments including mitochondria, whose cholesterol content is low compared to other cell membranes. Despite the limited availability of cho...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723000447 |
| _version_ | 1811154713450643456 |
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| author | Leire Goicoechea Laura Conde de la Rosa Sandra Torres Carmen García-Ruiz José C. Fernández-Checa |
| author_facet | Leire Goicoechea Laura Conde de la Rosa Sandra Torres Carmen García-Ruiz José C. Fernández-Checa |
| author_sort | Leire Goicoechea |
| collection | DOAJ |
| description | Cholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. Cholesterol traffics to different cellular compartments including mitochondria, whose cholesterol content is low compared to other cell membranes. Despite the limited availability of cholesterol in the inner mitochondrial membrane (IMM), the metabolism of cholesterol in the IMM plays important physiological roles, acting as the precursor for the synthesis of steroid hormones and neurosteroids in steroidogenic tissues and specific neurons, respectively, or the synthesis of bile acids through an alternative pathway in the liver. Accumulation of cholesterol in mitochondria above physiological levels has a negative impact on mitochondrial function through several mechanisms, including the limitation of crucial antioxidant defenses, such as the glutathione redox cycle, increased generation of reactive oxygen species and consequent oxidative modification of cardiolipin, and defective assembly of respiratory supercomplexes. These adverse consequences of increased mitochondrial cholesterol trafficking trigger the onset of oxidative stress and cell death, and, ultimately, contribute to the development of diverse diseases, including metabolic liver diseases (i.e. fatty liver disease and liver cancer), as well as lysosomal disorders (i.e. Niemann-Pick type C disease) and neurodegenerative diseases (i.e. Alzheimer's disease). In this review, we summarize the metabolism and regulation of mitochondrial cholesterol and its potential impact on liver and neurodegenerative diseases. |
| first_indexed | 2024-04-10T04:21:39Z |
| format | Article |
| id | doaj.art-5c33b5659d2148daafd8ffb459a44fbb |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-10T04:21:39Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-5c33b5659d2148daafd8ffb459a44fbb2023-03-11T04:19:39ZengElsevierRedox Biology2213-23172023-05-0161102643Mitochondrial cholesterol: Metabolism and impact on redox biology and diseaseLeire Goicoechea0Laura Conde de la Rosa1Sandra Torres2Carmen García-Ruiz3José C. Fernández-Checa4Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clinic i Provincial de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red (CIBEREHD), Barcelona, SpainDepartment of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clinic i Provincial de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red (CIBEREHD), Barcelona, SpainDepartment of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clinic i Provincial de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red (CIBEREHD), Barcelona, SpainDepartment of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clinic i Provincial de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red (CIBEREHD), Barcelona, Spain; Research Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA; Corresponding author. Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain.Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clinic i Provincial de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red (CIBEREHD), Barcelona, Spain; Research Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA; Corresponding author. Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain.Cholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. Cholesterol traffics to different cellular compartments including mitochondria, whose cholesterol content is low compared to other cell membranes. Despite the limited availability of cholesterol in the inner mitochondrial membrane (IMM), the metabolism of cholesterol in the IMM plays important physiological roles, acting as the precursor for the synthesis of steroid hormones and neurosteroids in steroidogenic tissues and specific neurons, respectively, or the synthesis of bile acids through an alternative pathway in the liver. Accumulation of cholesterol in mitochondria above physiological levels has a negative impact on mitochondrial function through several mechanisms, including the limitation of crucial antioxidant defenses, such as the glutathione redox cycle, increased generation of reactive oxygen species and consequent oxidative modification of cardiolipin, and defective assembly of respiratory supercomplexes. These adverse consequences of increased mitochondrial cholesterol trafficking trigger the onset of oxidative stress and cell death, and, ultimately, contribute to the development of diverse diseases, including metabolic liver diseases (i.e. fatty liver disease and liver cancer), as well as lysosomal disorders (i.e. Niemann-Pick type C disease) and neurodegenerative diseases (i.e. Alzheimer's disease). In this review, we summarize the metabolism and regulation of mitochondrial cholesterol and its potential impact on liver and neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S2213231723000447MitochondriaCholesterolROSMetabolismLiver diseaseNeurodegeneration |
| spellingShingle | Leire Goicoechea Laura Conde de la Rosa Sandra Torres Carmen García-Ruiz José C. Fernández-Checa Mitochondrial cholesterol: Metabolism and impact on redox biology and disease Redox Biology Mitochondria Cholesterol ROS Metabolism Liver disease Neurodegeneration |
| title | Mitochondrial cholesterol: Metabolism and impact on redox biology and disease |
| title_full | Mitochondrial cholesterol: Metabolism and impact on redox biology and disease |
| title_fullStr | Mitochondrial cholesterol: Metabolism and impact on redox biology and disease |
| title_full_unstemmed | Mitochondrial cholesterol: Metabolism and impact on redox biology and disease |
| title_short | Mitochondrial cholesterol: Metabolism and impact on redox biology and disease |
| title_sort | mitochondrial cholesterol metabolism and impact on redox biology and disease |
| topic | Mitochondria Cholesterol ROS Metabolism Liver disease Neurodegeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723000447 |
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