Mitochondria are 'stressed' and help cells survive respiratory infections?

Many respiratory infections, such as the flu or COVID-19, can place significant stress on cells and organs, leading to acute respiratory distress syndrome (ARDS), which itself can ultimately lead to death in elderly or sensitive individuals

Professor Johan Auwerx, from EPFL's School of Life Sciences, said: "New therapeutic strategies to address ARDS, rather than combating the source of infection, could induce tolerance to inflammatory challenges by enhancing the host organism's natural adaptive stress response

In a new study, EPFL's Adrienne Mottis and her colleagues show that one such strategy can exploit a biological phenomenon known as "mitochondrial hypoxemia

Mitochondria are the cell's main organelle for energy harvesting and are therefore constantly monitored by the cell's "surveillance" system

"Therefore, mild mitochondrial stress is beneficial for the cell and the organism as a whole, as the positive effects of these stress responses can overcome the negative effects of the initial stressor," said Mottis, who led the study

Because mitochondria evolved from bacteria, they are sensitive to antibiotics

The team of scientists screened 52 tetracyclines and selected new molecules, such as 9-tert-butyldoxycycline (9-TB), which are highly effective in triggering the mitochondrial hypostimulant effect even at low doses, while simultaneously There are no antibiotic side effects -- that is, they don't interfere with the host's microbiome

Auwerx added: "Most importantly, our study shows that 9-TB-triggered mitochondrial responses activate the ATF4 signaling pathway, a well-described response to multiple cellular stressors that also mobilizes innate immunity , the so-called type I interferon response

The study shows that 9-TB can induce tolerance to influenza infection in mice by reducing the degree of inflammation and tissue damage without affecting the mice's microbiota

Tetracycline-induced mitohormesis mediates disease tolerance against influenza