Mitochondrial Bioenergetics in Cancer and Immune Cells

Cancer and immune cells share the capacity to reprogramme their mitochondrial bioenergetics in response to microenvironmental cues. Tumour cells often engage aerobic glycolysis while retaining oxidative phosphorylation for biosynthetic and redox balance, a phenomenon that supports rapid proliferation and survival under hypoxia. Conversely, T cells and macrophages adopt distinct metabolic programmes during activation: effector T cells rely on glycolysis whereas memory and regulatory subsets reinvest in mitochondrial respiration and fatty acid oxidation. The dynamic interplay between glycolytic flux, tricarboxylic acid cycle activity and spare respiratory capacity underpins cell fate decisions, influences reactive oxygen species signalling and modulates responses to immunotherapies. Cross-talk within the tumour microenvironment further drives metabolic competition, whereby cancer-associated metabolic by-products and nutrient depletion can suppress antitumour immunity. Deciphering the mechanisms that govern substrate preference, mitochondrial dynamics and bioenergetic flexibility in these cell types has revealed novel targets to enhance cancer control and fine-tune immune interventions.

Research from Nature Portfolio

Recent studies have integrated high-content fluorescence imaging with extracellular flux measurements to yield a holistic view of mitochondrial function in single assays. By combining metabolic flux technology with multiplexed fluorescent dyes, researchers have simultaneously quantified cell proliferation, mitochondrial content, membrane potential, fragmentation state and reactive oxygen species. Application of this platform to pancreatic cancer models demonstrated that inhibition of coactivators driving mitochondrial biogenesis diminishes oxidative capacity and sensitises cells to chemotherapy. In breast cancer, modulation of Rho-GTPase signalling was shown to remodel mitochondrial dynamics and reduce spare respiratory capacity, thereby impairing metastatic potential. This integrated approach enhances reproducibility, allows normalisation to cell number and illuminates how genetic or pharmacological perturbations reshape bioenergetic landscapes in both malignant and stromal populations.

Mitochondrial Bioenergetics in Cancer and Immune Cells publication trend

The graph below shows the total number of articles in mitochondrial bioenergetics in cancer and immune cells across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative phosphorylation: Mitochondrial process coupling electron transport to ATP synthesis via proton gradients.

Glycolysis: Cytosolic breakdown of glucose to pyruvate with net ATP and NADH production, active under aerobic and anaerobic conditions.

Spare respiratory capacity: The difference between basal and maximal oxygen consumption, indicating mitochondrial resilience to stress.

Extracellular flux analysis: Measurement of oxygen consumption rate and extracellular acidification rate to infer cellular bioenergetics.

Metabolic flux assay: Technique integrating substrate injections and real-time measurements to map pathway activity and ATP generation.

References

1. IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway. Journal of Translational Medicine (2023).
2. Calculation of ATP production rates using the Seahorse XF Analyzer. EMBO Reports (2023).
3. High-content fluorescence imaging with the metabolic flux assay reveals insights into mitochondrial properties and functions. Communications Biology (2020).