Reduced Histone Expression or a Defect in Chromatin Assembly Induces Respiration

Abstract

Regulation of mitochondrial biogenesis and respiration is a complex process that involves several signaling pathways and transcription factors, as well as communication between the nuclear and mitochondrial genomes. Here we show that decreased expression of histones or a defect in nucleosome assembly in yeast result in increased mtDNA copy number, oxygen consumption, ATP synthesis, and expression of genes encoding enzymes of the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). The metabolic shift from fermentation to respiration induced by altered chromatin structure is associated with induction of the retrograde (RTG) pathway and requires the activity of the Hap2/3/4/5p complex as well as transport and metabolism of pyruvate in mitochondria. Together, our data indicate that altered chromatin structure relieves glucose repression of mitochondrial respiration by inducing transcription of the TCA cycle and OXPHOS genes encoded by both nuclear and mitochondrial DNA.