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Ago2 protects against diabetic cardiomyopathy via activating mitochondrial gene translation [Ribosome-seq]

ABSTRACT: Ago2 protects against diabetic cardiomyopathy via activating mitochondrial gene translation [Ribosome-seq]

PROVIDER: PRJNA1011229 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25824115_1.fastq.gz	Fastqsanger.gz
	SRR25824115_2.fastq.gz	Fastqsanger.gz
	SRR25824116_1.fastq.gz	Fastqsanger.gz
	SRR25824116_2.fastq.gz	Fastqsanger.gz
	SRR25824117_1.fastq.gz	Fastqsanger.gz

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Ago2 protects against diabetic cardiomyopathy via activating mitochondrial gene translation [Ribosome-seq]

Project description:Diabetes is associated with cardiovascular complications. microRNAs translocate into subcellular organelles to modify genes involved in diabetic cardiomyopathy. However, functional properties of subcellular Ago2, a core microRNA, remain elusive. We elucidated the function and mechanism of subcellular localized Ago2 on mouse models for diabetes mellitus and diabetic cardiomyopathy. Ago2 decreased in cardiomyocyte mitochondria in both models. Overexpression of mitochondrial Ago2 attenuated diabetes-induced cardiac dysfunction. Ago2 recruited TUFM, a mitochondria translation elongation factor, to activate translation of electron transport chain (ETC) subunits and decrease reactive oxygen species. Malonylation, a post-translational modification of Ago2, reduced the importing of Ago2 into mitochondria in diabetic cardiomyopathy. Ago2 malonylation was regulated by a cytoplasmic-localized short isoform of SIRT3 through a previously unknown demalonylase function. Our results reveal that the SIRT3–Ago2–CYTB axis links glucotoxicity to cardiac ETC imbalance, providing new mechanistic insights and the basis to develop mitochondria targeting therapies for diabetic cardiomyopathy.

2024-09-27 | GSE242024 | GEO

Ago2 protects against diabetic cardiomyopathy via activating mitochondrial gene translation

Project description:Ago2 protects against diabetic cardiomyopathy via activating mitochondrial gene translation

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Ago2 protects against diabetic cardiomyopathy via activating mitochondrial gene translation II

Project description:Ago2 protects against diabetic cardiomyopathy via activating mitochondrial gene translation II

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