Scientists have found enzymes that are activated in response to mitochondrial stress

Mitochondria are the strength of the cell. It plays a vital role in producing energy from food. In the meantime, it can be stressed and damaged.

Under stressful conditions, mitochondria activate their multiple defense mechanisms: biochemical “dominoes” that help them repair their deficiencies and recover or improve their health.

Mitochondria under stress are heavily involved in aging, cancer, neurodegenerative syndrome, and metabolic syndrome. Given how much central mitochondria are survival and health, they have improved a number of stress response pathways to adapt their function to a constantly changing cellular climate. However, how these stress responses are controlled remains largely unclear.

Now, scientists from EPFL have discovered certain enzymes that play a significant role in stress responses that defend mitochondria from stress and promote health and longevity. They found that stressed mitochondria cause global and very specific epigenetic changes, which include enzymes that uncover compacted DNA in the cell nucleus to activate genes. Known as histone acetyltransferase, these enzymes interact with histone proteins that package DNA into the chromatin structure.

Scientists have noticed chromatin nematode C. elegans; found that a histone acetyltransferase called CBP-1 plays a vital role in epigenetic changes caused by the mitochondrial response to stress. It translates their stress signal into the coordinated transcription of several genes known to be involved in the mitochondrial stress response.

Terytty Yang Li, the study’s first author, said “The beneficial effects of the mitochondrial response to stress, such as resistance to pathogenic infections, improved proteostasis against amyloid-β aggregation – one of the culprits of Alzheimer’s disease – and prolongation of life – depend almost entirely on these epigenetic changes. Moreover, analyzes in mouse and human populations, as well as genetic and pharmacological studies of loss of function in mammalian cells, strongly suggest that this epigenetic mechanism involved in regulating the response to stress, health, and life expectancy is also preserved in mice and humans. “

Johan Auwerx said, “Our work identifies an evolutionarily preserved node for mitochondrial stress signaling that defends mitochondrial function and promotes health and longevity. We are convinced that drugs that target these mitochondrial stress pathways may be of interest in combating the aging process. “

Journal reference:
  1. Terytty Yang Li et al. The CBP / p300 transcriptional coactivator is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress. Aging Nature, 2021. DOI: 10.1038 / s43587-020-00025-z