title: MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria.
abstract: 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.
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Aindrila
authors: A
authors: Chatterjee
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors: Janine
authors: J
authors: Seyfferth
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors: Jacopo
authors: J
authors: Lucci
authors: Institute for Experimental and Clinical Pharmacology and Toxicology, Abteilung II, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Ralf
authors: R
authors: Gilsbach
authors: Institute for Experimental and Clinical Pharmacology and Toxicology, Abteilung II, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Sebastian
authors: S
authors: Preissl
authors: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Lena
authors: L
authors: Böttinger
authors: Faculty of Biology, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany; Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Christoph U
authors: CU
authors: Mårtensson
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Amol
authors: A
authors: Panhale
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors: Thomas
authors: T
authors: Stehle
authors: BIOSS Centre for Biological Signalling Studies, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany; Renal Division, University Medical Center Freiburg, 79106 Freiburg, Germany.
authors: Oliver
authors: O
authors: Kretz
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors: Abdullah H
authors: AH
authors: Sahyoun
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors: Sergiy
authors: S
authors: Avilov
authors: Faculty of Biology, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany; Center for Systems Biology (ZBSA), Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Stefan
authors: S
authors: Eimer
authors: Institute for Experimental and Clinical Pharmacology and Toxicology, Abteilung II, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Lutz
authors: L
authors: Hein
authors: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Nikolaus
authors: N
authors: Pfanner
authors: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Thomas
authors: T
authors: Becker
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany. Electronic address: akhtar@ie-freiburg.mpg.de.
authors: Asifa
authors: A
authors: Akhtar
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D019069:Cell Respiration / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D044127:Epigenesis, Genetic; D006367:HeLa Cells; D006333:Heart Failure / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000201:enzymology / Q000235:genetics; D008931:Mitochondria, Muscle / Q000201:enzymology* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010085:Oxidative Phosphorylation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D047908:Intracellular Signaling Peptides and Proteins; C000607306:KANSL3 protein, human; C574033:NSL1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; C000622683:Kat8 protein, mouse
keywords: HAT; KANSL1; KANSL2; KANSL3; KAT; KAT8; KIAA1267; MOF; MSL1v1; MYST1; OXPHOS; acetylation; epigenetics; heart; mitochondria; mtDNA; respiration; transcription