The mitochondrial lactate oxidation complex: endpoint for carbohydrate carbon disposal

Area of Science:

• Cellular Metabolism
• Biochemistry
• Physiology

Background:

• The lactate shuttle concept reshaped understanding of cellular metabolism.
• The mitochondrial lactate oxidation complex (mLOC) structure was previously elucidated.
• Key components of mLOC include mLDH, mMCT, CD147, and COx.

Purpose of the Study:

• To identify additional components of the mitochondrial lactate oxidation complex (mLOC).
• To investigate the role of the mitochondrial pyruvate carrier (mPC) within the mLOC.
• To elucidate the architectural organization of the final carbohydrate oxidation pathway.

Main Methods:

• Immunoblotting and mass spectrometry of mitochondrial preparations.
• Co-immunoprecipitation experiments to identify protein interactions.
• Confocal laser scanning microscopy (CLSM) and in situ proximity ligation assays.

Main Results:

• Mitochondrial pyruvate carrier (mPC1 and mPC2) identified as a component of the mLOC in mouse muscle and C2C12 cells.
• Abundant presence of mLDH, mMCT, CD147, COx, and mPC confirmed in mitochondrial preparations.
• Demonstrated colocalization of pyruvate and lactate transporters with cytochrome oxidase (COx) in skeletal muscle.

Conclusions:

• The mitochondrial pyruvate carrier (mPC) is an integral part of the mitochondrial lactate oxidation complex (mLOC).
• This discovery refines the understanding of the architectural design of the mLOC.
• The mLOC plays a crucial role in establishing the concentration gradient for lactate and pyruvate disposal.