Mitochondria and cancer diagnosis

Abstract

Mitochondria, beyond their canonical role in ATP production, are central regulators of cancer metabolism, signaling, and progression. Research findings indicate a significant association between mitochondrial dysfunction and oncogenesis, affecting metabolic reprogramming, cellular plasticity, and therapeutic resistance. With important regulators such HIF-1α, PGC-1α, and AMPK dictating metabolic plasticity, mitochondrial metabolism in cancer shows a change between oxidative phosphorylation (OXPHOS) and aerobic glycolysis (Warburg effect). As tumor development, invasion, and chemoresistance are enhanced by oncogenic mitochondrial fission mediated by DRP1 and FIS1, apoptosis resistance is impacted by aberrant fusion regulated by MFN1, MFN2, and OPA1. Mitochondrial retrograde signaling, facilitated by ROS, NF-κB, ATF4, and UPRmt, enhances cancer progression and immune evasion by the reprogramming of nuclear gene expression. In breast, colorectal, and hepatocellular cancer, mtDNA mutations in the ND1, ND5, COX1, and CYTB genes are common. Mutations show their biomarker potential. Released circulating cell-free mtDNA (cf-mtDNA) into the circulation suggests a noninvasive approach to assessing tumor stage, oxidative damage (8-OHdG), and changes in mtDNA copy number. Additionally, changes to the tRNA and rRNA genes in the mitochondria affect translational efficiency, which leads to metabolic dysregulation in cancers. Using mitochondrial markers for cancer diagnosis offers creative ideas for precision oncology and could change early identification and prognostic evaluation. The present chapter highlights the critical importance of including biomarkers related to mitochondria in liquid biopsies to facilitate therapeutic approaches that target mitochondria.