AI Article Synopsis
- - Mitochondrial dysfunction causes cellular stress, prompting cells to activate survival responses to avoid dying, with changes in nuclear DNA methylation playing a crucial role.
- - Researchers examined how cellular stress responses like apoptosis and autophagy are affected by mitochondrial dysfunction, focusing on DNA methylation’s role in cell survival.
- - Experiments showed that in human muscle cells, severe mitochondrial dysfunction increases DNA methylation and activates pro-survival pathways, a finding supported by studies in tissues from mitochondrial disease patients.
Article Abstract
Mitochondrial dysfunction represents an important cellular stressor and when intense and persistent cells must unleash an adaptive response to prevent their extinction. Furthermore, mitochondria can induce nuclear transcriptional changes and DNA methylation can modulate cellular responses to stress. We hypothesized that mitochondrial dysfunction could trigger an epigenetically mediated adaptive response through a distinct DNA methylation patterning. We studied cellular stress responses (i.e., apoptosis and autophagy) in mitochondrial dysfunction models. In addition, we explored nuclear DNA methylation in response to this stressor and its relevance in cell survival. Experiments in cultured human myoblasts revealed that intense mitochondrial dysfunction triggered a methylation-dependent pro-survival response. Assays done on mitochondrial disease patient tissues showed increased autophagy and enhanced DNA methylation of tumor suppressor genes and pathways involved in cell survival regulation. In conclusion, mitochondrial dysfunction leads to a "pro-survival" adaptive state that seems to be triggered by the differential methylation of nuclear genes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11105675 | PMC |
| http://dx.doi.org/10.1007/s00018-019-03008-5 | DOI Listing |
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