Intracellular cholesterol transport proteins: roles in health and disease

Ugo Soffientini, Annette Graham

Research output: Contribution to journalArticle

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Abstract

Effective cholesterol homoeostasis is essential in maintaining cellular function, and this is achieved by a network of lipid-responsive nuclear transcription factors, and enzymes, receptors and transporters subject to post-transcriptional and post-translational regulation, whereas loss of these elegant, tightly regulated homoeostatic responses is integral to disease pathologies. Recent data suggest that sterol-binding sensors, exchangers and transporters contribute to regulation of cellular cholesterol homoeostasis and that genetic overexpression or deletion, or mutations, in a number of these proteins are linked with diseases, including atherosclerosis, dyslipidaemia, diabetes, congenital lipoid adrenal hyperplasia, cancer, autosomal dominant hearing loss and male infertility. This review focuses on current evidence exploring the function of members of the ‘START’ (steroidogenic acute regulatory protein-related lipid transfer) and ‘ORP’ (oxysterol-binding protein-related proteins) families of sterol-binding proteins in sterol homoeostasis in eukaryotic cells, and the evidence that they represent valid therapeutic targets to alleviate human disease.
Original languageEnglish
Pages (from-to)1843-1859
Number of pages17
JournalClinical Science
Volume130
Issue number21
Early online date22 Sep 2016
DOIs
Publication statusPublished - Nov 2016

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Sterols
Carrier Proteins
Homeostasis
Cholesterol
Health
Adrenal Gland Neoplasms
Lipids
Sequence Deletion
Male Infertility
Eukaryotic Cells
Dyslipidemias
Hearing Loss
Atherosclerosis
Proteins
Transcription Factors
Pathology
Enzymes
Therapeutics

Keywords

  • cholesterol
  • homoeostasis
  • cellular function

Cite this

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abstract = "Effective cholesterol homoeostasis is essential in maintaining cellular function, and this is achieved by a network of lipid-responsive nuclear transcription factors, and enzymes, receptors and transporters subject to post-transcriptional and post-translational regulation, whereas loss of these elegant, tightly regulated homoeostatic responses is integral to disease pathologies. Recent data suggest that sterol-binding sensors, exchangers and transporters contribute to regulation of cellular cholesterol homoeostasis and that genetic overexpression or deletion, or mutations, in a number of these proteins are linked with diseases, including atherosclerosis, dyslipidaemia, diabetes, congenital lipoid adrenal hyperplasia, cancer, autosomal dominant hearing loss and male infertility. This review focuses on current evidence exploring the function of members of the ‘START’ (steroidogenic acute regulatory protein-related lipid transfer) and ‘ORP’ (oxysterol-binding protein-related proteins) families of sterol-binding proteins in sterol homoeostasis in eukaryotic cells, and the evidence that they represent valid therapeutic targets to alleviate human disease.",
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Intracellular cholesterol transport proteins: roles in health and disease. / Soffientini, Ugo; Graham, Annette.

In: Clinical Science, Vol. 130, No. 21, 11.2016, p. 1843-1859.

Research output: Contribution to journalArticle

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