Mitochondrial Metabolism in Cancer Cells

Cancer cells reprogramme mitochondrial functions to support rapid proliferation, survive environmental stresses and resist therapy. Beyond their classical role in ATP generation through oxidative phosphorylation, mitochondria supply biosynthetic precursors—such as lipids, nucleotides and amino acids—via the tricarboxylic acid cycle and interconnected pathways. They regulate redox balance by managing reactive oxygen species and orchestrate calcium signalling and apoptosis. Tumour cells adapt mitochondrial dynamics, striking a balance between fission and fusion, to meet fluctuating energy demands and maintain organelle quality. Hypoxic regions within tumours elicit stabilisation of hypoxia-inducible factors, further reshaping mitochondrial enzyme expression and promoting glycolytic flux alongside residual respiration. This metabolic flexibility underpins invasive potential, metastatic spread and immune evasion. Consequently, mitochondria have emerged as both crucial mediators of oncogenic processes and attractive targets for novel anticancer strategies.

Research from Nature Portfolio

Recent studies have illuminated how transcriptional regulators intersect with mitochondrial metabolism to curb tumour growth. Work on cutaneous squamous cell carcinoma has uncovered a suppressor that binds glycolytic gene promoters, impeding the interaction of a key hypoxia-driven factor and lowering expression of enzymes essential for glucose uptake and conversion. The result is a marked reduction in glycolytic throughput and a shift towards oxidative metabolism that diminishes cancer cell proliferation in vitro and in vivo. This regulatory axis offers a blueprint for designing therapies that restore mitochondrial control over energy pathways in tumours that rely on aberrant glycolysis.

Mitochondrial Metabolism in Cancer Cells publication trend

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

Technical terms

Oxidative phosphorylation (OXPHOS): Process by which mitochondria generate ATP through electron transport and chemiosmotic coupling.

Electron transport chain (ETC): Series of protein complexes in the inner mitochondrial membrane that transfer electrons and pump protons to drive ATP synthesis.

Warburg effect: Propensity of cancer cells to ferment glucose into lactate even in the presence of oxygen, reflecting altered energy metabolism.

Hypoxia-inducible factor (HIF): Transcription factor stabilised under low oxygen that regulates genes controlling metabolism, angiogenesis and survival.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that modulate signalling but can cause damage at high levels.

Mitochondrial dynamics: The balance of organelle fission and fusion that maintains mitochondrial function, morphology and distribution.

References

1. Mitochondrial metabolism and cancer. Cell Research (2017).
2. Mitochondria as biosynthetic factories for cancer proliferation. Cancer & Metabolism (2015).
3. HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development. Nature Communications (2018).
4. Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer. Cells (2021).
5. Mitochondria Targeting as an Effective Strategy for Cancer Therapy. International Journal of Molecular Sciences (2020).