The DOI matches its Crossref record; 186 of the 186 references it cites were found in a registry or an index.
Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function
Abstract
Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology.
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“The ER is well known in steroidogenic research as the site of action of numerous steroidogenic CYP and HSD/KSR enzymes (3), but recently, the ER has attracted recent interest in mitochondrial cholesterol metabolism as a possible source of cholesterol (147).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [147]
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Self-citation
Metadata
- Authors
- Martin, L. A., Kennedy, B. E., & Karten, B.
- Affiliations
- Dalhousie University (CA)
- Corresponding author
- Karten, Barbara
- ORCID
- Karten, Barbara
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2014-11-26
- Volume
- 48
- Issue
- 2
- Pages
- 137-151
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W1993948951
- Cited by
- 128
- References
- 186
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 10 · 2023: 13 · 2022: 21 · 2021: 20 · 2020: 9 · 2019: 10 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 3 · 2014: 1
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Bioenergetics and Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- mitochondrial cholesterol, steroidogenic acute regulatory protein, mitochondria-associated ER membranes, lipid transfer proteins, mitochondrial function, oxysterols, bile acids, mitochondrial membrane
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Animals, Biological Transport, Active, Cholesterol, Endoplasmic Reticulum, Humans, Mitochondria, Phosphoproteins, Mitochondrial Membranes
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