An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Abstract

Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD + /NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.

Nontoxic Fluorescent Nanoprobes for Multiplexed Detection and 3D Imaging of Tumor Markers in Breast Cancer

“…Mutations in mitochondrial DNA are commonly found in cancer cells and promote the rewiring of bioenergetics and biosynthesis of various metabolites, including oncometabolites. For more details, you can read the overview about role of mitochondria in cancer metabolism written by Liu et al [ 64 ]. Chen et al summarized more detailed information on mutations and epigenetic regulation of mitochondrial DNA and its impact on mismanagement of reactive oxygen species cascade and its association with cancer prognosis as well as usage of mutations and epigenetic modifications of mitochondrial DNA as viable markers for early diagnosis and targeted therapy of BC [ 65 ].…”

Ribosome Biogenesis Regulator 1 Homolog (RRS1) Promotes Cisplatin Resistance by Regulating AEG-1 Abundance in Breast Cancer Cells

“…Breast cancer overlook lung cancer as the most frequently diagnosed cancer worldwide in 2020, accounting for nearly 12% of new cases [ 1 ]. Breast cancer cells show metabolic abnormalities and mitochondrial oxidative stress, and various tumor marker proteins are increased [ 2 , 3 , 4 ]. A combination of preoperative chemotherapy and surgery is the current treatment strategy for breast cancer patients.…”

The Association between Early-Onset Diagnosis and Clinical Outcomes in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

“…Driver mutations in over 30 cancer genes have been implicated in breast cancer, including AKT1 , BRCA1 , CDH1 , GATA3 , PIK3C , PTEN , RB1 , and TP53 [ 7 , 8 ]. Genetic and epigenetic changes also confer interactions between tumour cells and nearby tissue to facilitate tumour microenvironments that support tumour progression and metastasis [ 9 ]. Changes in the tumour microenvironment induce alterations in gene expression to adjust metabolic requirements of tumours for better adaptation.…”

“…Changes in the tumour microenvironment induce alterations in gene expression to adjust metabolic requirements of tumours for better adaptation. For example, mitochondrial activity is reduced to consume oxygen in hypoxic conditions and generate energy through oxidative phosphorylation [ 9 , 10 ].…”