The Role of Mitochondria in the Development and Progression of Lung Cancer

Abstract

The influence of mitochondria in human health and disease is a rapidly expanding topic in the scientific literature due to their integral roles in cellular death and survival. Mitochondrial biology and alterations in function were first linked to cancer in the 1920s with the discovery of the Warburg effect. The utilization of aerobic glycolysis in ATP synthesis was the first of many observations of metabolic reprogramming in cancer.Mitochondrial dysfunction in cancer has expanded to include defects in mitochondrial genomics and biogenesis, apoptotic signaling and mitochondrial dynamics. This review will focus on the role of mitochondria and their influence on cancer initiation, progression and treatment in the lung.

Mitochondria in lung disease

“…ALI and ARDS result from the inflammatory response of the lung to both direct and indirect insults and are characterized by severe hypoxemia, hypercapnia, diffuse infiltration visible in the chest x-ray, and a substantial reduction in pulmonary compliance (45). Mitochondrial biogenesis is increased in bronchial smooth muscle remodeling in asthma (46) and in lung cancer; however, in lung cancer, it is unclear whether these alterations contribute to tumorigenesis or are a consequence of carcinogenesis (47). In contrast, loss of mitochondrial biogenesis is associated with COPD, which may be associated with a significantly lower body mass index and lower muscle mass (ref.…”

“…In contrast, loss of mitochondrial biogenesis is associated with COPD, which may be associated with a significantly lower body mass index and lower muscle mass (ref. 48 and (44) PGC1-α and TFAM increased after S. aureus sepsis in the distal lung (44) Increased in ALI, pneumonia, hyperoxia (43) Increased upon S. aureus-associated sepsis (44), may be associated with resolution of lung injury (42) Increased in bronchial smooth muscle remodeling in asthma (46) Increased in lung cancer (47) Reduced in COPD, which may be associated with a significantly lower body mass index and less muscle mass (48) (53), and loss of PINK1 and defective mitophagy promote pulmonary fibrosis (PF) in animal models and in human idiopathic pulmonary fibrosis (IPF) (54,55). PF is characterized by irreversible destruction of lung architecture, abnormal wound healing, and deposition of extracellular matrix (ECM) proteins, leading to disruption of gas exchange and death from respiratory failure.…”

Multi‐regional sequencing reveals intratumor heterogeneity and positive selection of somatic mtDNA mutations in hepatocellular carcinoma and colorectal cancer

“…When compared with nuclear DNA, mtDNA has a higher mutation rate due to high reactive oxygen species (ROS) level, deficiency of DNA repair system and lack of histone protection in mitochondria. To date, mtDNA mutations have been found in various cancer cells . Moreover, a series of studies have documented critical roles for mtDNA mutations in the initiation, metastasis and metabolic changes of cancer cells .…”

Bacillus spp.: Attractive Sources of Anti-cancer and Anti-proliferative Biomolecules

“…Although, EMT causes the conversion of the epithelial cells into mesenchymal cells through loss of cell polarity, the recent observation implies the critical role of EMT in tumor progression and modulation of an early stage tumor into an invasive malignancy (Yeo et al, 2017). is hypoxic microenvironment can also be generated by mitochondrial dysfunction where the mitochondrial metabolites accumulate in the cytoplasm due to the imbalance between glycolysis and oxidative phosphorylation (Roberts & Jean, 2013).…”