Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints.
Nat Commun
; 9(1): 2221, 2018 06 07.
Article
em En
| MEDLINE
| ID: mdl-29880867
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Paraganglioma
/
Estresse Fisiológico
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Complexo II de Transporte de Elétrons
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Metabolismo Energético
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Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article