Targeting Mitochondrial Pyruvate Carrier: Impact on Future Metabolic Therapies
Prof. Edmund Kunji from the University of Cambridge will give a major talk entitled Targeting mitochondrial pyruvate carrier: impact on future metabolic therapies, during the Targeting Mitochondria 2025 Congress, which will be held on October 22-24, in Berlin, Germany.
About Prof. Kunji's talk:
Fifty years after the mitochondrial pyruvate carrier (MPC) was first identified, researchers have now resolved its molecular structure and mechanism of action. In a landmark study published in Science Advances, Sichrovsky et al. (2025) unveiled how this critical mitochondrial complex mediates pyruvate transport and how its inhibition could be leveraged for therapeutic purposes in cancer, metabolic disorders, and more.
About his outstanding study:
Major Discoveries of the Study by Prof. Edmund Kunji and his teams
Molecular Structure of MPC:
The authors used cryo-electron microscopy to capture the architecture of the human MPC complex. They discovered that MPC forms a heterodimeric transport unit (MPC1/MPC2), creating a selective channel that guides pyruvate across the inner mitochondrial membrane.
Mechanism of Transport and Inhibition:
The study revealed how small-molecule inhibitors bind to the MPC complex and block its function, offering a blueprint for drug development. Structural analysis pinpointed specific binding sites that explain both transport dynamics and inhibition sensitivity.
Conserved Functionality:
Evolutionary conservation of the MPC mechanism across species (including yeast and human) underscores its universal biological role in cellular energy homeostasis.
Therapeutic Implications
Cancer:
Some tumors overexpress MPC to fuel high mitochondrial activity. MPC inhibitors could starve these cells of essential metabolites, selectively disrupting their growth.
Metabolic Diseases:
In conditions like non-alcoholic fatty liver disease (NAFLD), blocking MPC forces hepatocytes to burn fat instead of relying on glucose, leading to reduced liver fat accumulation.
Regenerative Medicine & Hair Growth:
MPC inhibition has been shown to stimulate lactate production, which may promote hair follicle cell activation, opening potential new treatments for alopecia.
Mitochondrial Dysfunction & Neurodegeneration:
Targeting MPC may allow modulation of energy metabolism in neurodegenerative and mitochondrial diseases, where ATP production and redox balance are impaired.
Broader Impact
Drug Development:
The structural elucidation of MPC provides a molecular framework for designing selective modulators, setting the stage for new classes of metabolic drugs.
Precision Medicine:
Understanding individual differences in MPC structure/function may lead to personalized metabolic therapies tailored to genetic or disease-specific metabolic profiles.
Synthetic Biology & Bioenergetics:
The detailed MPC model can inform the engineering of customized metabolic pathways, supporting advances in synthetic biology, cell therapies, and biotechnology.
