Cited by 128Cholesterol and Lipid MetabolismMitochondrial Function and PathologyCancer, Lipids, and Metabolism

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Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function

Martin, Laura A., Kennedy, Barry E., Karten, Barbara·2016·Journal of Bioenergetics and Biomembranes

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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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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
Publisher: Springer Science and Business Media LLC
Published: 2014-11-26
Volume: 48
Issue: 2
Pages: 137-151
ISSN: 0145-479X (ISSN-L)
1573-6881
DOI: 10.1007/s10863-014-9592-6
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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Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function

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