The mitochondrion as a mechanometabolic conductor of cancer metastasis: pharmacological insights from the mitochondria–peroxisome interface
- 1Department of Biochemistry and Molecular Cell Biology (IBMZ), Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf
- 2Department of Molecular Biology, Ariel University
Abstract
Metastasis demands more than sustained ATP production: cancer cells must move organelles, remodel membranes, manage oxidative stress, and reprogram metabolism as they pass from invasion to distant colonisation. Mitochondria sit at the centre of this adaptation. This Review organises their contribution around four linked axes: deployment to the cell cortex and invadopodia; reactive oxygen species and metabolite signalling; VDAC1-dependent metabolite, calcium, apoptotic and mtDNA gating; and HIF-1α–BNIP3-dependent remodelling of the mitochondrial pool. We then ask how this mitochondrial programme is altered by peroxisomes. The two organelles share components of the fission machinery, coordinate lipid-derived substrate use and cellular redox balance, and divide tasks in hydrogen-peroxide control, ether-lipid synthesis, organelle quality control and MAVS signalling. These connections matter pharmacologically. A DRP1- or redox-directed intervention may affect both organelles, whereas VDAC1 provides a more mitochondria-restricted target logic. Peroxisomal pathways are also context dependent: fatty-acid shortening and ether-lipid synthesis can increase metabolic flexibility and membrane remodelling, yet the same pathways may raise oxidative stress or create ferroptotic susceptibility. By separating established molecular links from mechanisms that remain untested in metastatic models, we propose a hierarchical view in which mitochondria remain the principal mechanometabolic conductor, while peroxisomes set important boundary conditions for substrate use, redox signalling, immune responses and therapeutic selectivity. We also state the limitation this framing carries. The mitochondrial arm of the framework rests on direct experimental evidence, whereas a causal contribution of mitochondria–peroxisome contacts to invasion, transit or colonisation has not been demonstrated: it is inferred here from contact biology characterised without testing metastatic endpoints, from division machinery shared between the two organelles, and from biochemical coupling. The interface is therefore advanced as a testable framework for target selection and pharmacological attribution, not as an established driver of metastasis.
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BibTeX
@article{dutta2026mitochondrion,
title = {{The mitochondrion as a mechanometabolic conductor of cancer metastasis: pharmacological insights from the mitochondria–peroxisome interface}},
author = {Subhajit Dutta and Namrata Maity},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1983363},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1983363/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The mitochondrion as a mechanometabolic conductor of cancer metastasis: pharmacological insights from the mitochondria–peroxisome interface
AU - Subhajit Dutta
AU - Namrata Maity
PY - 2026
DA - 2026/10/27
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1983363
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1983363/full
AB - Metastasis demands more than sustained ATP production: cancer cells must move organelles, remodel membranes, manage oxidative stress, and reprogram metabolism as they pass from invasion to distant colonisation. Mitochondria sit at the centre of this adaptation. This Review organises their contribution around four linked axes: deployment to the cell cortex and invadopodia; reactive oxygen species and metabolite signalling; VDAC1-dependent metabolite, calcium, apoptotic and mtDNA gating; and HIF-1α–BNIP3-dependent remodelling of the mitochondrial pool. We then ask how this mitochondrial programme is altered by peroxisomes. The two organelles share components of the fission machinery, coordinate lipid-derived substrate use and cellular redox balance, and divide tasks in hydrogen-peroxide control, ether-lipid synthesis, organelle quality control and MAVS signalling. These connections matter pharmacologically. A DRP1- or redox-directed intervention may affect both organelles, whereas VDAC1 provides a more mitochondria-restricted target logic. Peroxisomal pathways are also context dependent: fatty-acid shortening and ether-lipid synthesis can increase metabolic flexibility and membrane remodelling, yet the same pathways may raise oxidative stress or create ferroptotic susceptibility. By separating established molecular links from mechanisms that remain untested in metastatic models, we propose a hierarchical view in which mitochondria remain the principal mechanometabolic conductor, while peroxisomes set important boundary conditions for substrate use, redox signalling, immune responses and therapeutic selectivity. We also state the limitation this framing carries. The mitochondrial arm of the framework rests on direct experimental evidence, whereas a causal contribution of mitochondria–peroxisome contacts to invasion, transit or colonisation has not been demonstrated: it is inferred here from contact biology characterised without testing metastatic endpoints, from division machinery shared between the two organelles, and from biochemical coupling. The interface is therefore advanced as a testable framework for target selection and pharmacological attribution, not as an established driver of metastasis.
SN - 1663-9812
ER -