Steroidogenic Regulation of Cholesterol Transport in Mitochondrial Systems
Summary
The biosynthesis of steroid hormones hinges on the regulated delivery of cholesterol from intracellular stores to the inner mitochondrial membrane, where cytochrome P450 side-chain cleavage enzyme initiates conversion to pregnenolone. Cholesterol traverses the cytosol and engages specialised transport proteins at the outer mitochondrial membrane, most notably the steroidogenic acute regulatory protein (StAR), which facilitates lipid desorption and intermembrane transfer. This acute step is complemented by chronic transcriptional programmes controlling mitochondrial biogenesis and expression of lipid-handling factors. Recent work highlights a coordinated network involving START-domain proteins, mitochondrial scaffolding factors, autophagic pathways and lipid droplet dynamics, all converging to fine-tune cholesterol availability in response to trophic signals. Emerging evidence also implicates mitochondrial chaperones and membrane contact sites in sculpting sterol microdomains, thereby optimising substrate access for steroidogenic enzymes and safeguarding cellular homeostasis under fluctuating hormonal demand.
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Steroidogenic Regulation of Cholesterol Transport in Mitochondrial Systems publication trend
The graph below shows the total number of articles in steroidogenic regulation of cholesterol transport in mitochondrial systems across all publications each year (not limited to Nature Index journals).
Technical terms
Steroidogenesis: The enzymatic process by which cholesterol is converted into steroid hormones in specialised cells.
StAR (Steroidogenic Acute Regulatory protein): A mitochondrial outer-membrane protein that initiates the rate-limiting step of cholesterol import for steroid hormone synthesis.
START domain: A conserved lipid-binding module in proteins that facilitates the selective transfer of sterols and phospholipids between membranes.
Autophagy: A cellular catabolic pathway that degrades and recycles organelles and macromolecules, contributing to lipid mobilisation.
Lipophagy: A selective form of autophagy targeting lipid droplets to release stored cholesterol esters and triglycerides.
References
- Membrane specificity of the human cholesterol transfer protein STARD4. Journal of Molecular Biology (2024).
- The Expanding Role of Mitochondria, Autophagy and Lipophagy in Steroidogenesis. Cells (2021).
- Early steps in steroidogenesis: intracellular cholesterol trafficking Thematic Review Series: Genetics of Human Lipid Diseases. Journal of Lipid Research (2011).
- Steroidogenic Acute Regulatory Protein (StAR) Is A Sterol Transfer Protein*. Journal of Biological Chemistry (1998).
- Steroidogenic Acute Regulatory Protein Binds Cholesterol and Modulates Mitochondrial Membrane Sterol Domain Dynamics*. Journal of Biological Chemistry (2001).
- Role of Constitutive STAR in Leydig Cells. International Journal of Molecular Sciences (2021).
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