This article presents a comprehensive study on the mitochondrial pyruvate carrier (MPC), detailing six cryo-electron microscopy (cryo-EM) structures of the protein complex in three distinct states. The findings, which include highest resolution structures of MPC in various orientations, elucidate the transport mechanism of pyruvate into the mitochondria, essential for the TCA cycle. The study emphasizes the significance of structural transitions and the interactions of the MPC with inhibitory compounds like UK5099, providing crucial insights into its function and potential as a therapeutic target.
The study unveils six different cryo-EM structures of the human mitochondrial pyruvate carrier (MPC) showcasing its mechanisms in transporting pyruvate for cellular metabolism.
Our data reveal that the mitochondrial pyruvate carrier transitions through various states, illustrating an intricate alternating access mechanism crucial for effective substrate transport.
The introduction of the UK5099 inhibitor reveals how it fits into a specific pocket on the MPC, suggesting vital implications for metabolic regulation and therapeutic intervention.
The reported structures provide a clearer understanding of the MPC, enhancing the comprehension of its role in mitochondrial function and metabolism.
#cryoelectron-microscopy #mitochondrial-pyruvate-carrier #substrate-transport #structural-biology #metabolism
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