MOF acetyl transferase regulates transcription and respiration in mitochondria
Chatterjee A, Seyfferth J, Lucci J, Gilsbach R, Preissl S, Böttinger L, Mårtensson CU, Panhale A, Stehle T, Kretz O, Sahyoun AH, Avilov S, Eimer S, Hein L, Pfanner N, Becker T, Akhtar A.
The nuclear MYST family acetyl transferase MOF regulates transcription of nuclear genes. Unexpectedly, we found that a pool of MOF together with a subset of non-specific lethal complex proteins localize to mitochondria. MOF regulates expression of nuclear genes involved in oxidative phosphorylation. In addition, MOF binds to the mitochondrial DNA to regulate the transcription of mitochondrial genes. The binding to the mitochondrial DNA depends on its partner protein KANSL3. Loss of MOF affects mitochondrial metabolism. The respiratory defects and impaired transcription of mitochondrial genes can be rescued by a mitochondrial targeted version of MOF. However, mitochondrial localized catalytic inactive MOF does not rescue the respiratory defect indicating that the acetyl transferase activity of MOF is required in mitochondria. A conditional knockout mouse reveals severe defects in tissues with high energy demands like cardiomyocytes. These cells show mitochondrial degeneration and deregulation of mitochondrial metabolism. Thus, MOF is dually localized to control expression of nuclear and mitochondrial genes linking epigenetics and metabolism.
