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Alternate assembly of SDHA connects energy stress to metabolic checkpoint and DNA synthesis

ABSTRACT: Alternate assembly of SDHA connects energy stress to metabolic checkpoint and DNA synthesis

OTHER RELATED OMICS DATASETS IN: PXD009656

PROVIDER: PRJNA429204 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6451710.fastq.gz	Fastqsanger.gz
	SRR6451711.fastq.gz	Fastqsanger.gz
	SRR6451704.fastq.gz	Fastqsanger.gz
	SRR6451705.fastq.gz	Fastqsanger.gz
	SRR6451706.fastq.gz	Fastqsanger.gz

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Alternate assembly of SDHA connects energy stress to metabolic checkpoint and DNA synthesis

Project description:Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. We have discovered that an alternative mitochondrial complex II (CII) assembly, designated here as CIIlow, serves as a check-point for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings uncover a new core complex inside mitochondria that provides homeostatic control of cellular metabolism to reflect availability of energy, with SDHA being its central molecule.

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Respiratory complex II - Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints

Project description:Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints

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Rad53 checkpoint kinase couples leading and lagging strand DNA synthesis

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Cardiolipin Synthesis Governs Systemic Energy Homeostasis through Thermogenic Fat Mitochondria

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Project description:Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

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