The capacity of mitochondria to produce ATP via oxidative phosphorylation, regulate cellular metabolism, maintain calcium homeostasis, and control apoptosis. Mitochondrial function encompasses ATP production efficiency, mitochondrial biogenesis, dynamics (fusion/fission), and quality control (mitophagy).
Mitochondria oxidize substrates (glucose, fatty acids, amino acids) through TCA cycle, generating NADH and FADH2. Electron transport chain (complexes I-IV) transfers electrons to oxygen, pumping protons across inner membrane. Proton gradient drives ATP synthase (complex V) producing ATP. Mitochondrial function regulated by PGC-1Ξ± (biogenesis), AMPK and sirtuins (energy sensors), fusion proteins (MFN1/2, OPA1) and fission proteins (DRP1), and mitophagy machinery (PINK1/Parkin). Dysfunction manifests as reduced ATP, increased ROS, impaired calcium buffering, and dysregulated apoptosis.
Mitochondrial dysfunction underlies most chronic diseases: neurodegeneration, metabolic syndrome, chronic fatigue, cardiovascular disease, cancer, aging. In cPNI, assessment includes clinical signs (fatigue, exercise intolerance, cognitive dysfunction), labs (lactate, organic acids), and response to interventions. Improving mitochondrial function requires: substrates (CoQ10, B vitamins, magnesium, carnitine), hormesis (exercise, fasting, cold/heat), toxin reduction, inflammation resolution, and thyroid optimization.
- Adult humans have ~10 million billion mitochondria (~10% body weight)
- Brain and heart have highest mitochondrial density
- ATP production: ~50-70 kg ATP per day at rest
- Efficiency: ~30-40% of energy captured as ATP (rest as heat)
- mtDNA: 37 genes encoding 13 ETC subunits; maternally inherited
- Mitochondria generate 90% of cellular ROS as byproduct
- Mitochondrial biogenesis stimulated by exercise, fasting, cold
- NAD+/NADH ratio critical for mitochondrial function; declines with age
- PGC-1Ξ± is master regulator of mitochondrial biogenesis
- Mitophagy removes dysfunctional mitochondria; impaired in aging
- ATP production β Primary function; oxidative phosphorylation generates cellular energy
- oxidative phosphorylation β Process by which mitochondria generate ATP using oxygen
- electron transport chain β Series of complexes in inner membrane generating proton gradient
- TCA cycle β Mitochondrial cycle oxidizing acetyl-CoA to generate NADH/FADH2
- PGC-1Ξ± β Master transcriptional coactivator inducing mitochondrial biogenesis
- AMPK β Energy sensor activating PGC-1Ξ± and mitochondrial biogenesis
- NAD+ β Essential cofactor for mitochondrial metabolism; declines with age
- sirtuins β NAD+-dependent deacetylases regulating mitochondrial function
- ROS β Mitochondria major source; excessive ROS damages mitochondria
- exercise β Potent stimulator of mitochondrial biogenesis via PGC-1Ξ±
- fasting β Activates AMPK and sirtuins, promoting mitochondrial biogenesis
- aging β Mitochondrial dysfunction central mechanism of aging
- neurodegeneration β Mitochondrial dysfunction implicated in Alzheimer's, Parkinson's
- chronic fatigue syndrome β Often characterized by mitochondrial dysfunction
- thyroid hormones β T3 directly regulates mitochondrial biogenesis and function
- inflammation β Chronic inflammation impairs mitochondrial function
- calcium β Mitochondria buffer calcium; overload triggers apoptosis
- apoptosis β Mitochondria control cell death via cytochrome c release
- mitophagy β Quality control mechanism removing damaged mitochondria
- CoQ10 β Essential electron carrier in ETC; supplementation may improve function
- Module 1
- Module 2
- Module 3