Mitochondria: Endosymbiont bacteria DNA sequence as a target against cancer

Abstract

As the energy factory for the cell, the mitochondrion, through its role of adenosine triphosphate production by oxidative phosphorylation, can be regarded as the guardian of well regulated cellular metabolism; the integrity of mitochondrial functions, however, is particularly vulnerable in cancer due to the lack of superstructures such as histone and lamina folds to protect the mitochondrial genome from unintended exposure, which consequently elevates risks of mutation. In cancer, mechanisms responsible for enforcing quality control surveillance for identifying and eliminating defective mitochondria are often poorly regulated, and certain uneliminated mitochondrial DNA (mtDNA) mutations and polymorphisms can be advantageous for the proliferation, progression, and metastasis of tumor cells. Such pathogenic mtDNA aberrations are likely to increase and occasionally be homoplasmic in cancer cells and, intriguingly, in normal cells in the proximity of tumor microenvironments as well. Distinct characteristics of these abnormalities in mtDNA may provide a new path for cancer therapy. Here we discuss a promising novel therapeutic strategy, using the sequence‐specific properties of pyrrole‐imidazole polyamide‐triphenylphosphonium conjugates, against cancer for clearing abnormal mtDNA by reactivating mitochondrial quality control surveillance.

Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

“…In this way, defective mitophagy caused by mtDNA mutations may contribute to the development of chronic diseases, including cancers, neurodegenerative diseases, and metabolic disorders. [144][145][146] Therefore, it is important to understand the relationship between mutations in mtDNA, mitochondrial dysfunction, and mitophagy defects. Mitochondrial DNA mutations were found to be associated with atherosclerosis.…”

The Entanglement between Mitochondrial DNA and Tumor Metastasis

“…The unlimited proliferation ability of cancer cells results in their craving for ATP and metabolites. Mitochondria are crucial for oxidizing glucose, fats and amino acids to release energy through the tricarboxylic acid (TCA) cycle and OXPHOS [4], which is thought to be the "energy factory" of cancer cells [5]. The transfer mitochondria from aggressively growing tumors to less aggressive tumors can cause an increase in tumor aggressiveness, indicating the critical role of mitochondria in determining the cancer cell biology [6].…”