Year: 2025
Type: article
Abstract: Conventional wisdom holds that nuclear oncogenes and tumor suppressors initiate malignant transformation. However, mounting research suggests that mitochondrial dysfunction—rooted in the unique evolutionary history and genetic autonomy of mitochondria—may serve as a more fundamental driver of oncogenesis. This paper proposes a “mitochondria-first” hypothesis of cancer, emphasizing the pivotal role of mitochondrial DNA (mtDNA) mutations, metabolic reprogramming, and immune evasion. By examining the evolutionary conflict between host and mitochondria, evaluating high mtDNA mutation rates, and highlighting the disruptive potential of mitochondrial transfer to immune cells, we outline robust mechanisms through which mitochondria could ignite cancer development. We also discuss emerging diagnostic and therapeutic approaches that target mitochondrial integrity, offering a potential paradigm shift in oncology.
Source: Onco
DOI: 10.3390/onco5030032
Author: Sergio Da Silva
Institution: Universidade Federal de Santa Catarina
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,207
OpenAlex ID: W4411901994