Related Experiment Video
Updated: May 13, 2025

07:56
Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
4.1K
STAR/STARD1: a mitochondrial intermembrane space cholesterol shuttle degraded through mitophagy
Biorxiv : the Preprint Server for Biology
|April 16, 2025
Summary
The steroidogenic acute regulatory protein (STAR) acts as a shuttle, moving cholesterol to mitochondria for hormone synthesis. This study reveals STAR
Area of Science:
- Mitochondrial biology
- Steroidogenesis
- Cellular metabolism
Background:
- Cholesterol import into mitochondria is vital for steroid hormone and bile acid synthesis.
- The precise mechanism and components of this cholesterol transport process remain debated.
- The steroidogenic acute regulatory protein (STAR/STARD1) is a key player in this process.
Purpose of the Study:
- To elucidate the mitochondrial import machinery and structural aspects of STAR.
- To reveal STAR's role in cholesterol transport and its subsequent fate.
- To provide a mechanistic basis for STAR mutation-related diseases.
Main Methods:
- Structural biology techniques to determine STAR's structure.
- Biochemical assays to study cholesterol transport.
- Cellular imaging and degradation assays.
Main Results:
- STAR functions as an intermembrane space cholesterol shuttle.
- STAR is rapidly degraded by mitophagy after cholesterol transfer.
- This mechanism explains STAR's pulsatile activity and disease mutations.
Conclusions:
- STAR's shuttle function and mitophagy-mediated degradation are fundamental to mitochondrial cholesterol import.
- This provides a new framework for understanding steroidogenesis and lipoid congenital adrenal hyperplasia.
Related Concept Videos
Translocation of Proteins into the Mitochondria
3.0K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Mitochondrial Protein Sorting
4.1K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.1K
Protein Transport into the Inner Mitochondrial Membrane
3.5K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
3.5K
Mitochondrial Precursor Proteins
2.5K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.5K
The Inner Mitochondrial Membrane
3.2K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.2K
Export of Misfolded Proteins out of the ER
3.3K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.3K

