MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria

Chatterjee, Aindrilla; Seyfferth, Janine; Lucci, Jacopo; Glisbach, Ralf; Preissl, Sebastian; Böttinger, Lena; Martensson, Christoph U.; Panhale, Amol; Stehle, Thomas; Kretz, Oliver; Sahyoun, Abdullah H.; Avilov, Sergiy; Eimer, Stefan; Hein, Lutz; Pfanner, Nicolaus; Becker, Thomas; Akhtar, Asifa

doi:10.1016/j.cell.2016.09.052

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学術論文

MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria

MPS-Authors

Chatterjee, Aindrilla
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Seyfferth, Janine
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Lucci, Jacopo
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Panhale, Amol
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Stehle, Thomas
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sahyoun, Abdullah H.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Avilov, Sergiy
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Akhtar, Asifa
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S009286741631337X?via%3Dihub
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引用

Chatterjee, A., Seyfferth, J., Lucci, J., Glisbach, R., Preissl, S., Böttinger, L., Martensson, C. U., Panhale, A., Stehle, T., Kretz, O., Sahyoun, A. H., Avilov, S., Eimer, S., Hein, L., Pfanner, N., Becker, T., & Akhtar, A. (2016). MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria. Cell, 167, 722-738. doi:10.1016/j.cell.2016.09.052.

引用: https://hdl.handle.net/11858/00-001M-0000-002C-AF24-2

要旨

A functional crosstalk between epigenetic regulators and metabolic control could provide a mechanism to adapt cellular responses to environmental cues. We report that the well-known nuclear MYST family acetyl transferase MOF and a subset of its non-specific lethal complex partners reside in mitochondria. MOF regulates oxidative phosphorylation by controlling expression of respiratory genes from both nuclear and mtDNA in aerobically respiring cells. MOF binds mtDNA, and this binding is dependent on KANSL3. The mitochondrial pool of MOF, but not a catalytically deficient mutant, rescues respiratory and mtDNA transcriptional defects triggered by the absence of MOF. Mof conditional knockout has catastrophic consequences for tissues with high-energy consumption, triggering hypertrophic cardiomyopathy and cardiac failure in murine hearts; cardiomyocytes show severe mitochondrial degeneration and deregulation of mitochondrial nutrient metabolism and oxidative phosphorylation pathways. Thus, MOF is a dual-transcriptional regulator of nuclear and mitochondrial genomes connecting epigenetics and metabolism.