Prohibitin Functions in Mitochondrial Biology and Cancer

Prohibitins, comprising PHB1 and PHB2 subunits, form a high‐molecular‐weight scaffold within the inner mitochondrial membrane, playing pivotal roles in maintaining mitochondrial architecture, respiratory chain integrity and mitochondrial DNA stability. By organising membrane lipids and stabilising respiratory complexes, prohibitins regulate oxidative phosphorylation and mitochondrial dynamics, thereby influencing cellular energy metabolism, reactive oxygen species production and apoptosis. Beyond their mitochondrial functions, prohibitins shuttle to the nucleus or cytosol to modulate transcriptional programmes, cell‐cycle progression and signal transduction pathways such as PI3K/Akt and ERK/MAPK. In cancer, aberrant prohibitin expression exerts context‐dependent effects: elevated PHB2 can promote tumour cell proliferation, survival and metastatic potential via modulation of mitochondrial bioenergetics and oncogenic signalling, whereas in certain settings prohibitin loss sensitises cells to apoptosis and impairs tumour growth. The duality of prohibitin function underscores its global significance as both a biomarker of mitochondrial health and a prospective therapeutic target. Interventions that disrupt prohibitin–protein interactions or alter prohibitin‐mediated scaffold assembly hold promise for restoring mitochondrial homeostasis and inhibiting malignancy. Advances in structural biology and live‐cell imaging continue to reveal how prohibitins integrate mitochondrial quality control with nuclear transcriptional networks, offering new avenues for precision therapies in mitochondrial disorders and cancer.

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Prohibitin Functions in Mitochondrial Biology and Cancer publication trend

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

Technical terms

Prohibitin: A hetero‐oligomeric complex of PHB1 and PHB2 in the mitochondrial inner membrane that scaffolds respiratory complexes and regulates mitochondrial morphology.

Oxidative phosphorylation (OXPHOS): The process by which electrons transferred through the mitochondrial electron transport chain drive ATP synthesis via ATP synthase.

Ubiquitination: The covalent attachment of ubiquitin to a target protein, marking it for proteasomal degradation or altering its cellular function.

E3 ubiquitin ligase: An enzyme that recognises substrate proteins and catalyses the transfer of ubiquitin from an E2 enzyme to the substrate.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen, produced as by‐products of mitochondrial respiration, which can signal or cause oxidative damage.

Mitochondrial complex I: The first multisubunit enzyme complex of the electron transport chain, responsible for oxidising NADH and initiating proton translocation.

References

1. PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer. Journal of Experimental & Clinical Cancer Research (2024).
2. PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation. Cell Death & Disease (2023).
3. UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis. Journal of Translational Medicine (2024).
4. Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases. Cells (2019).
5. Essential Protein PHB2 and Its Regulatory Mechanisms in Cancer. Cells (2023).