Cellular respiration

Cellular respiration is a fundamental biological process that converts stored chemical energy (glucose) into usable energy (ATP), which is essential for all cellular activities.

Steps of Cellular Respiration

The process unfolds in three main stages:

Glycolysis: Glucose is broken down into pyruvate, yielding a small amount of ATP.

Citric Acid Cycle (Krebs Cycle): Pyruvate is further oxidized, producing some ATP and electron carriers (NADH, FADH2).

Oxidative phosphorylation (OXPHOS): Oxidative phosphorylation is centered on the electron transport chain (ETC), where electrons move through protein complexes in the mitochondrial membrane. This movement releases energy, which is used to pump protons across the membrane, creating a gradient. The gradient drives ATP synthesis via ATP synthase. Oxygen serves as the final electron acceptor, combining with electrons and protons to form water. This process is the primary source of ATP in cellular respiration.

 

Cancer Cells' Altered Metabolism

Cancer cells often prefer anaerobic respiration (glycolysis) even in the presence of oxygen, a phenomenon known as the Warburg effect. This metabolic shift contributes to cancer progression and survival. 

However, many cancers still rely on mitochondrial metabolism (including Complex I) for the generation of metabolic intermediates, ATP, and maintenance of redox balance.

Complex I (NADH oxidoreductase) is the first and largest enzyme of the mitochondrial electron transport chain (ETC). It plays a key role in cellular energy production by catalyzing the transfer of electrons from NADH to coenzyme Q (ubiquinone), ultimately driving the synthesis of ATP through oxidative phosphorylation (OXPHOS). 

In many cancers, particularly aggressive and metastatic ones, glycolysis and OXPHOS are used in parallel to meet energy demands and biosynthetic needs. This metabolic flexibility allows cancer cells to adapt to their environment, making them resilient to nutrient deprivation, hypoxia, and therapeutic interventions.

Inhibition of one pathway (e.g., glycolysis) often leads to compensatory upregulation of the other (e.g., OXPHOS), making combined metabolic targeting an attractive therapeutic strategy.