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.

Keywords: apoptosis; mitochondrial dynamics; mitochondrial dysfunction; non-small cell lung cancer; tumorigenesis.

Figure 1

Altered bioenergetics and genomic instability in lung cancer. This comparison shows lung cancer alterations in bioenergetic signaling pathways, including a shift towards the reduced production of ATP using glycolysis instead of oxidative phosphorylation and the consequential impact on cancer initiation and progression. Additionally, mitochondrial dysfunction that occurs as a by-product of altered bioenergetics is displayed showing how genomic instability promotes tumorigenesis.

Figure 2

Mitochondrial pathways: interactions between apoptotic signaling and mitochondrial dynamics. Visualized is the complex array of proteins and signaling molecules that are involved in normal apoptotic signaling, both extrinsic and intrinsic, and the interaction of mitochondrial dynamics players that modify mitochondrial morphology and consequentially impact apoptotic regulation. Green colored text indicates pro-apoptotic signaling and red colored text indicates anti-apoptotic signaling.