Role of mitochondrial alterations in human cancer progression and cancer immunity

Abstract

Dysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, cellular metabolism, apoptosis, and calcium and redox homeostasis. Although the “Warburg effect,” in which cancer cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to cancer progression is still unclear. This review discusses recent progress in the alterations of mitochondrial DNA (mtDNA) and mitochondrial dynamics in cancer malignant progression. Moreover, we integrate the possible regulatory mechanism of mitochondrial dysfunction–mediated mitochondrial retrograde signaling pathways, including mitochondrion-derived molecules (reactive oxygen species, calcium, oncometabolites, and mtDNA) and mitochondrial stress response pathways (mitochondrial unfolded protein response and integrated stress response) in cancer progression and provide the possible therapeutic targets. Furthermore, we discuss recent findings on the role of mitochondria in the immune regulatory function of immune cells and reveal the impact of the tumor microenvironment and metabolism remodeling on cancer immunity. Targeting the mitochondria and metabolism might improve cancer immunotherapy. These findings suggest that targeting mitochondrial retrograde signaling in cancer malignancy and modulating metabolism and mitochondria in cancer immunity might be promising treatment strategies for cancer patients and provide precise and personalized medicine against cancer.

ELUCIDATION OF THE ROLE OF miRNA 4263 IN DYSREGULATED MITOCHONDRIAL ENERGETICS AND CARCINOGENESIS

“…By modifying mitochondrial metabolism, cancer cells change how they produce energy in more advanced stages of the disease. (Sheng-Fan Wang et.al, 2023). In a variety of cancer, the glycolytic pathway has been reported as an alternate mode of energy, employed by the cancer cells for their exponential growth.…”

“…MicroRNAs could be a key player in the suppression of expression pattern of the crucial mitochondrial genes involved in electron transport chain (ETC), thereby altering the rate of ATP generation (Wee Lin Tan et.al, 2023). Several malignancies have been reported to have altered mitochondrial machinery together with elevated amounts of oncogenic microRNAs (Sheng-Fan Wang et.al, 2023). MicroRNA 4263 is an important oncomiR reported to be found at higher levels in exosomes derived from hypoxic tumor colony of HCC and plays an important role in carcinogenesis by inducing angiogenesis, an important hallmark of cancer (Sruthi TV, 2019).…”

Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy

“…Mitochondria are essential organelles of living cells to produce energy and they also maintain cellular homeostasis and regulate cell death pathways. − Mitochondrial dysfunction is also known to activate several mitochondrial retrograde signaling and mitochondrial stress response pathways, which promote cancer progression to malignancy. − Therefore, targeting mitochondrial function has emerged as a potential therapeutic strategy against cancer. Currently, several drugs that target mitochondrial metabolism and/or induce mitochondrial apoptosis have been investigated. − Nevertheless, small-molecule ligands specifically targeting G4-mtDNA and capable of regulating mitochondrial metabolism and apoptosis are rarely found.…”

Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions

“…Accelerated aging in cancer survivors can be attributed to cancer itself and cancer treatment [ 1 , 3 , 4 , 5 , 6 ]. The accumulation of stress induced by cancer and its treatment may incite hallmarks of aging, such as cellular senescence, inflammation, telomere shortening, epigenetic alterations, and mitochondrial dysfunction [ 2 , 7 ]. These hallmarks of aging are interconnected with each other and contribute to accelerated aging [ 8 ].…”