Abstract
Mitochondria are major cellular organelles that play an essential role in metabolism, stress response, immunity, and cell fate. Mitochondria are organized in a network with other cellular compartments, functioning as a signaling hub to maintain cells’ health. Mitochondrial dysfunctions and genome alterations are associated with diseases including cancer. Mitochondria are a preferential target for pathogens, which have developed various mechanisms to hijack cellular functions for their benefit. Helicobacter pylori is recognized as the major risk factor for gastric cancer development. H. pylori induces oxidative stress and chronic gastric inflammation associated with mitochondrial dysfunction. Its pro-apoptotic cytotoxin VacA interacts with the mitochondrial inner membrane, leading to increased permeability and decreased ATP production. Furthermore, H. pylori induces mitochondrial DNA damage and mutation, concomitant with the development of gastric intraepithelial neoplasia as observed in infected mice. In this chapter, we present diverse aspects of the role of mitochondria as energy supplier and signaling hubs and their adaptation to stress conditions. The metabolic activity of mitochondria is directly linked to biosynthetic pathways. While H. pylori virulence factors and derived metabolites are essential for gastric colonization and niche adaptation, they may also impact mitochondrial function and metabolism, and may have consequences in gastric pathogenesis. Importantly, during its long way to reach the gastric epithelium, H. pylori faces various cellular types along the gastric mucosa. We discuss how the mitochondrial response of these different cells is affected by H. pylori and impacts the colonization and bacterium niche adaptation and point to areas that remain to be investigated.
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Acknowledgements
We are grateful to Dr. Manuel Amieva (Stanford University, CA, USA) for providing excellent photos of human and mouse gastric mucosa (Figs. 2 and 3). This work is supported by Odyssey Reinsurance and Institut Pasteur Transversal Research Programs to ET (PTRs 217 and 332-20). The figures were created with BioRender.com.
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Torres, J., Touati, E. (2023). Mitochondrial Function in Health and Disease: Responses to Helicobacter pylori Metabolism and Impact in Gastric Cancer Development. In: Backert, S. (eds) Helicobacter pylori and Gastric Cancer. Current Topics in Microbiology and Immunology, vol 444. Springer, Cham. https://doi.org/10.1007/978-3-031-47331-9_3
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