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Published on: January 11, 2017
miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway
Jincheng Li1, Stefan Donath, Yanrui Li
1Department of Physiology, Shantou University School of Medicine, Shantou, China.
Abstract:
miRNAs participate in the regulation of apoptosis. However, it remains largely unknown as to how miRNAs are integrated into the apoptotic program. Mitochondrial fission is involved in the initiation of apoptosis. It is not yet clear whether miRNAs are able to regulate mitochondrial fission. Here we report that miR-30 family members are able to regulate apoptosis by targeting the mitochondrial fission machinery. Our data show that miR-30 family members can inhibit mitochondrial fission and the consequent apoptosis. In exploring the underlying molecular mechanism, we identified that miR-30 family members can suppress p53 expression. In response to the apoptotic stimulation, the expression levels of miR-30 family members were reduced, whereas p53 was upregulated. p53 transcriptionally activated the mitochondrial fission protein, dynamin-related protein-1 (Drp1). The latter conveyed the apoptotic signal of p53 by initiating the mitochondrial fission program. miR-30 family members inhibited mitochondrial fission through suppressing the expression of p53 and its downstream target Drp1. Our data reveal a novel model in which a miRNA can regulate apoptosis through targeting the mitochondrial fission machinery.
Insights
MicroRNAs (miRNAs) regulate apoptosis by targeting mitochondrial fission. The miR-30 family inhibits mitochondrial fission and apoptosis by suppressing p53 and Drp1 expression, revealing a novel regulatory pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of cellular processes, including apoptosis.
- The precise mechanisms integrating miRNAs into apoptotic pathways remain incompletely understood.
- Mitochondrial fission is an early event in apoptosis, but its regulation by miRNAs is unclear.
Purpose of the Study:
- To investigate whether miRNAs can regulate mitochondrial fission.
- To elucidate the role of the miR-30 family in apoptosis.
- To identify the molecular mechanisms by which miRNAs control mitochondrial fission-mediated apoptosis.
Main Methods:
- Analysis of miRNA expression levels during apoptosis.
- Investigating the effect of miR-30 family members on mitochondrial fission.
- Assessing the impact of miR-30 on p53 and dynamin-related protein-1 (Drp1) expression.
- Utilizing molecular biology techniques to study gene regulation and protein interactions.
Main Results:
- miR-30 family members were found to inhibit mitochondrial fission and subsequent apoptosis.
- miR-30 family members suppress the expression of p53.
- p53 upregulates the expression of dynamin-related protein-1 (Drp1), a key mediator of mitochondrial fission.
- miR-30 inhibits apoptosis by targeting the p53-Drp1 axis, thereby controlling mitochondrial fission.
Conclusions:
- The miR-30 family regulates apoptosis by targeting the mitochondrial fission machinery.
- A novel pathway is revealed where miRNAs control apoptosis through modulation of mitochondrial fission.
- This study provides new insights into the complex interplay between miRNAs, p53, Drp1, and apoptosis.
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