Short-Term Mitochondrial Permeability Transition Pore Opening Modulates Histone Lysine Methylation at the Early Phase of Somatic Cell Reprogramming.
Cell Metab
; 28(6): 935-945.e5, 2018 12 04.
Article
em En
| MEDLINE
| ID: mdl-30174306
ABSTRACT
Reprogramming of somatic cells to induced pluripotent stem cells reconfigures chromatin modifications. Whether and how this process is regulated by signals originating in the mitochondria remain unknown. Here we show that the mitochondrial permeability transition pore (mPTP), a key regulator of mitochondrial homeostasis, undergoes short-term opening during the early phase of reprogramming and that this transient activation enhances reprogramming. In mouse embryonic fibroblasts, greater mPTP opening correlates with higher reprogramming efficiency. The reprogramming-promoting function of mPTP opening is mediated by plant homeodomain finger protein 8 (PHF8) demethylation of H3K9me2 and H3K27me3, leading to reduction in their occupancies at the promoter regions of pluripotency genes. mPTP opening increases PHF8 protein levels downstream of mitochondrial reactive oxygen species production and miR-101c and simultaneously elevates levels of PHF8's cofactor, α-ketoglutarate. Our findings represent a novel mitochondria-to-nucleus pathway in cell fate determination by mPTP-mediated epigenetic regulation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Histonas
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Proteínas de Transporte da Membrana Mitocondrial
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Membranas Mitocondriais
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Reprogramação Celular
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Histona Desmetilases
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Fibroblastos
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Células-Tronco Embrionárias Murinas
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Lisina
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Mitocôndrias
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article