What is 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. This complex metabolic pathway ensures that cells have the energy needed to perform vital functions including growth, repair, and maintenance.

Steps of Cellular Respiration

The process unfolds in three main stages, each with distinct functions and locations within the cell:

Stage 1: Glycolysis

Glucose is broken down into pyruvate in the cytoplasm, yielding a small amount of ATP and NADH. This stage occurs without oxygen and represents the first step in energy extraction from glucose.

Stage 2: Citric Acid Cycle (Krebs Cycle)

Pyruvate is further oxidized in the mitochondrial matrix, producing some ATP and electron carriers (NADH, FADH2). This cycle completes the oxidation of glucose-derived carbon atoms.

Stage 3: 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 in Cancer Metabolism

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).

Metabolic Flexibility in Cancer

Parallel Pathway Usage

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.

Compensatory Mechanisms

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 for cancer treatment.