Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress, 2018, Lee et al

Andy · Jul 7, 2018

Highlights

•MOTS-c, a peptide encoded by the mitochondrial DNA, can localize to the nucleus

•Metabolic stress triggers AMPK-dependent translocation of MOTS-c to the nucleus

•MOTS-c can bind to chromatin and regulate nuclear gene expression

•MOTS-c can promote cellular stress resistance against metabolic stress

Summary

Cellular homeostasis is coordinated through communication between mitochondria and the nucleus, organelles that each possess their own genomes. Whereas the mitochondrial genome is regulated by factors encoded in the nucleus, the nuclear genome is currently not known to be actively controlled by factors encoded in the mitochondrial DNA. Here, we show that MOTS-c, a peptide encoded in the mitochondrial genome, translocates to the nucleus and regulates nuclear gene expression following metabolic stress in a 5′-adenosine monophosphate-activated protein kinase (AMPK)-dependent manner. In the nucleus, MOTS-c regulated a broad range of genes in response to glucose restriction, including those with antioxidant response elements (ARE), and interacted with ARE-regulating stress-responsive transcription factors, such as nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2). Our findings indicate that the mitochondrial and nuclear genomes co-evolved to independently encode for factors to cross-regulate each other, suggesting that mitonuclear communication is genetically integrated.
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Paywalled at https://www.cell.com/cell-metabolism/abstract/S1550-4131(18)30390-5

Article on the study

USC researchers focused on the two parts of the cell that carry DNA: the nucleus and the mitochondria. Most genetic material resides in the nucleus, which is the largest component of the cell. Its DNA sends coded templates telling the cell what to do. Smaller mitochondria function as energy-producing factories, turning food into fuel to power the cell. But size can be misleading. The mitochondria also contain DNA, all of it inherited from the mother, and as the new study shows, they are not just taking orders from the nucleus.

Working with human cells, the scientists discovered that when a cell is under stress and starved for nutrients, MOTS-c, a small protein encoded in the mitochondria DNA, moves into the nucleus to control genes and turn on a defensive system, including an antioxidant response.

“Most diseases are due to aging, and aging leads to a breakdown in cell functions,” Lee said. “When things go wrong in the body, it’s because some mechanism in the body went wrong. So, understanding how cells age means we have more insight into how the damage occurs and how we can prevent or fix it,” he said.
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https://news.usc.edu/145046/mitochondrial-dna-nuclear-dna-work-together-usc-study/

alktipping · Jul 7, 2018

an article that can be understood by lay people or even me . makes a nice change instead of having to reread it several times .

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Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress, 2018, Lee et al

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Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress, 2018, Lee et al

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