Lactate as a fuel for mitochondrial respiration

Area of Science:

• Exercise Physiology
• Skeletal Muscle Metabolism

Background:

• Lactate production in skeletal muscle is debated, historically linked to fatigue and hypoxia.
• Skeletal muscle is now recognized for both lactate production and clearance, prompting interest in its metabolic fate.
• Lactate isotopes reveal skeletal muscle extracts lactate despite net release, with enhanced oxidation during exercise.

Purpose of the Study:

• To synthesize current understanding of skeletal muscle lactate metabolism.
• To re-evaluate the role of lactate dehydrogenase (LDH) and cellular factors in lactate turnover.
• To present a comprehensive model of lactate metabolism in skeletal muscle at rest and during exercise.

Main Methods:

• Review and synthesis of existing literature on skeletal muscle lactate.
• Analysis of studies using lactate isotopes to track metabolic fate.
• Examination of the role of lactate dehydrogenase (LDH) isoforms and cellular localization.

Main Results:

• Skeletal muscle exhibits significant lactate uptake and oxidation, enhanced by exercise.
• Lactate dehydrogenase (LDH) activity and isoform function are crucial for lactate turnover.
• Cellular compartmentalization and LDH association with structures influence lactate-pyruvate balance.

Conclusions:

• Skeletal muscle lactate metabolism is complex, involving both production and clearance.
• Cellular factors, including LDH compartmentalization, are key regulators of lactate turnover.
• A unified model integrating transport, uptake, release, and oxidation is proposed for skeletal muscle lactate metabolism.