Related Experiment Video
Updated: Jun 20, 2026
07:35
Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
An Evolutionarily Conserved TUSC2-OSCP Interface Suggests a Mitochondrial Ca2⁺-Sensing Mechanism for ATP Synthase
Sergey V Ivanov1, Roman V Uzhachenko1, Sergei P Budko2
1Department of Biochemistry, Cancer Biology, Neuroscience, and Pharmacology, School of Medicine, Meharry Medical College, 1005 D.B. Todd Jr. Blvd, Nashville, TN 37208, USA.
Journal of Molecular Biology
|June 18, 2026
Summary
TUSC2, a mitochondrial calcium-binding protein, may regulate ATP synthase and the permeability transition pore. This interaction, conserved across species, could be key to understanding neurodegenerative diseases.
Area of Science:
- Mitochondrial biology
- Biochemistry
- Structural biology
Background:
- Mitochondrial ATP synthase (mATPS) regulates the mitochondrial permeability transition pore (mPTP) during calcium (Ca²⁺) fluctuations.
- Dysregulation of this process is linked to neurodegenerative diseases, but the underlying mechanisms are unclear.
- TUSC2 loss causes mitochondrial Ca²⁺ overload and mPTP opening, suggesting its role in Ca²⁺ sensing.
Purpose of the Study:
- To investigate the interaction between TUSC2 and the oligomycin sensitivity-conferring protein (OSCP), a regulatory subunit of mATPS.
- To elucidate the structural and evolutionary basis of TUSC2's role in mATPS regulation and Ca²⁺ sensing.
Main Methods:
- AI-assisted structural modeling (AlphaFold3)
- Phylogenetic analysis
- Bioinformatic analysis of conserved protein regions
Main Results:
- TUSC2 is nominated as a novel OSCP-interacting partner.
- Structural modeling predicts Ca²⁺-dependent binding between TUSC2's conserved motif and OSCP's C-terminal region.
- This interaction interface is evolutionarily conserved across diverse species, suggesting a fundamental regulatory role.
Conclusions:
- TUSC2 plays a conserved, Ca²⁺-sensing regulatory role in mATPS function.
- The findings provide a structural basis for TUSC2-OSCP interaction and its implications for mPTP regulation.
- This research offers insights into potential therapeutic targets for age-related and neurodegenerative diseases.
Keywords:
OSCP (ATP5PO)TUSC2 (FUS1)calcium-binding motifmetal ion coordinationmitochondrial ATP synthaseMore Related Videos
Related Concept Videos
01:48ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
01:18ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
01:37Energy to Drive Translocation
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:22Chemiosmosis and ATP Synthesis
The electron transport chain is a critical component of cellular respiration, occurring in the inner mitochondrial membrane. It facilitates the transfer of high-energy electrons from reduced cofactors NADH and FADH₂ to molecular oxygen, the final electron acceptor. This transfer of electrons through a series of protein complexes is tightly coupled to the translocation of protons across the membrane, generating a proton gradient essential for ATP synthesis.Electron Flow and Proton...
01:43Electron Transport Chain: Complex III and IV
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...