Mitochondrial orchestration of melanoma: A nexus of metabolism, immunity, and therapeutic vulnerability.

Authors

Patrycja Kłos, Siarhei Dabravolski

Published in

Mitochondrion. Pages 102224. Oct 12, 2026. Epub Oct 12, 2026.

Abstract

Despite therapeutic advances, melanoma remains a lethal malignancy characterised by profound therapeutic resistance. Emerging evidence positions the mitochondrion not as a subordinate organelle but as a central command centre orchestrating the key hallmarks of the disease. This review synthesises the profound dysregulation of the melanoma mitochondrial landscape, detailing the shift from a simple Warburg model to a nuanced understanding of metabolic plasticity, the critical role of organellar dynamics, and the dual function of reactive oxygen species (ROS) as both damaging agents and vital signalling molecules. We explore how this rewired state provides the bioenergetic and biosynthetic currency for proliferation and is essential for the arduous process of metastasis, a journey facilitated by novel mechanisms of intercellular mitochondrial transfer. Critically, the mitochondrion serves as the decisive battleground at the tumour-immune interface. While melanoma cells actively sabotage T-cell mitochondrial fitness to drive immune exhaustion, the metabolic state of the tumour's own mitochondria dictates its immunogenicity and susceptibility to immune attack. This deep mechanistic insight has unveiled a rich portfolio of therapeutic strategies, from direct bioenergetic inhibitors and mitochondria-targeted nanomedicines to innovative modalities such as photodynamic immunotherapy and mitochondrial transplantation, which offer powerful avenues to overcome therapy resistance. Finally, we discuss the burgeoning potential of mitochondrial features as prognostic and predictive biomarkers, arguing that a holistic, systems-level view is essential for paving the way towards a new era of personalised 'mito-oncology' to combat this devastating disease.

PMID:
42863551
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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