Related Experiment Video
Updated: Jun 10, 2026
06:07
Histological Examination of Mitochondrial Morphology in a Parkinson's Disease Model
Published on: June 23, 2023
Alpha-synuclein fibrils induce budding of mitochondrial-derived vesicles
Thomas Braun1, Viviane Reber2, Cinzia Tiberi3
1Biozentrum, University of Basel, Basel 4056, Switzerland.
Summary
Alpha-synuclein (α-syn) fibrils damage mitochondria, causing defects in cristae structure and increasing mitochondrial-derived vesicle (MDV) budding. This suggests a novel link between α-syn aggregation and mitochondrial dysfunction in neurodegenerative diseases.
Area of Science:
- Neurobiology
- Cell Biology
- Mitochondrial Biology
Background:
- Alpha-synuclein (α-syn) aggregation is a key feature of synucleinopathies like Parkinson's disease (PD).
- Mitochondrial dysfunction is implicated in PD pathogenesis, but the precise mechanisms linking α-syn to mitochondrial toxicity are unclear.
Purpose of the Study:
- To investigate the impact of α-syn fibrils on mitochondrial structure and function.
- To explore the relationship between α-syn aggregation and mitochondrial-derived vesicle (MDV) formation.
Main Methods:
- High-resolution electron microscopy of SH-SY5Y cells exposed to α-syn fibrils.
- Structural proteomics analysis using mass spectrometry.
Main Results:
- Exposure to α-syn fibrils induced defects in mitochondrial cristae structure.
- Increased budding of mitochondrial-derived vesicles (MDVs) was observed in cells with α-syn fibrils.
- Proteomics identified changes in proteins regulating mitochondrial structure and vesicle formation.
Conclusions:
- Alpha-synuclein fibrils may promote MDV generation, highlighting a significant link between α-syn and mitochondrial health.
- These findings offer insights into potential diagnostic and therapeutic strategies for synucleinopathies.
Related Concept Videos
01:45Vesicular Tubular Clusters
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
01:39Mitochondrial Protein Sorting
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...
01:19Translocation of Proteins into the Mitochondria
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,...
01:38Intralumenal Vesicles and Multivesicular Bodies
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
01:12Porin Insertion in the Outer Mitochondrial Membrane
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
01:39Mitochondrial Precursor Proteins
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 precursors...
Most of the mitochondrial precursors...