Mitochondrial oxygen affinity predicts basal metabolic rate in humans

Area of Science:

• Human Physiology
• Mitochondrial Biology
• Metabolic Research

Background:

• Basal metabolic rate (BMR) varies significantly between individuals, even after accounting for factors like body weight and thyroid hormones.
• The underlying mechanisms driving these interindividual BMR differences remain largely unknown.
• Mitochondria are central to cellular energy production, and their function is critical for BMR.

Purpose of the Study:

• To investigate the mechanistic determinants of interindividual variation in human basal metabolic rate (BMR).
• To explore the relationship between mitochondrial oxygen affinity and BMR.
• To identify factors controlling mitochondrial oxygen affinity in human skeletal muscle.

Main Methods:

• Measurement of mitochondrial oxygen affinity (p50(mito)) in isolated human skeletal muscle mitochondria.
• Correlation analysis between p50(mito) and mass-related BMR.
• Assessment of oxygen affinity and efficiency during submaximal exercise.
• Investigation of the role of cytochrome c oxidase (COX) excess in regulating p50(mito) using cyanide inhibition.

Main Results:

• Mass-related BMR strongly correlated with mitochondrial oxygen affinity (p50(mito)) in humans (R(2)=0.66).
• Similar correlations were observed between oxygen affinity and exercise efficiency (R(2)=0.46).
• BMR did not correlate with mitochondrial density or proton leak, but p50(mito) was influenced by COX protein levels and activity.

Conclusions:

• Interindividual variation in human BMR is primarily determined by differences in mitochondrial oxygen affinity.
• Mitochondrial oxygen affinity, potentially regulated by COX excess, plays a crucial role in metabolic rate.
• These findings suggest a trade-off between aerobic efficiency and metabolic power in humans.