miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway

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...

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Bibliographic Details
Published in:PLoS genetics 2010-01, Vol.6 (1), p.e1000795-e1000795
Main Authors: Li, Jincheng, Donath, Stefan, Li, Yanrui, Qin, Danian, Prabhakar, Bellur S, Li, Peifeng
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Base Sequence
Biochemistry/Transcription and Translation
Cardiomyocytes
Cells, Cultured
Dynamins - genetics
Dynamins - metabolism
Fibroblasts - metabolism
Gene Expression Regulation
Genetic aspects
Heart attacks
Hydrogen peroxide
MicroRNA
MicroRNAs - genetics
MicroRNAs - metabolism
Mitochondria
Mitochondria - genetics
Mitochondria - metabolism
Molecular Biology/Post-Translational Regulation of Gene Expression
Molecular Biology/RNA-Protein Interactions
Molecular Biology/Translation Mechanisms
Molecular Sequence Data
Physiological aspects
Physiology/Cell Signaling
Proteins
Rats
Rats, Wistar
Sequence Homology, Nucleic Acid
Signal Transduction
Tumor suppressor genes
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1000795