MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria
MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria
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DOI：
10.1016/j.cell.2016.09.052
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发表时间：
2016-10-20
期刊：
影响因子：
64.5
通讯作者：
Akhtar, Asifa
中科院分区：
文献类型：
--
作者：
Chatterjee, Aindrila;Seyfferth, Janine;Akhtar, Asifa
表观遗传调节和代谢控制之间的功能串扰可以提供一种机制，以适应细胞反应的环境线索。我们报告说，众所周知的核MYST家族乙酰转移酶MOF和其非特异性致命的复杂的合作伙伴的一个子集居住在线粒体。在有氧呼吸细胞中，MOF通过控制来自核和mtDNA的呼吸基因的表达来调节氧化磷酸化。MOF结合mtDNA，并且这种结合依赖于KANSL 3。MOF的线粒体池，但不是催化缺陷突变体，拯救呼吸和线粒体DNA转录缺陷引发的MOF的情况下。MOF条件性敲除对高能量消耗的组织具有灾难性后果，在小鼠心脏中引发肥厚型心肌病和心力衰竭;心肌细胞显示严重的线粒体变性和线粒体营养代谢和氧化磷酸化途径的失调。因此，MOF是连接表观遗传学和代谢的核和线粒体基因组的双重转录调节因子。
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; cardiomyo-cytes 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.