Aconitase couples metabolic regulation to mitochondrial DNA maintenance.
Mitochondrial DNA (mtDNA) is essential for cells to maintain respiratory competency and is inherited as a protein-DNA complex called the nucleoid. We have identified 22 mtDNA-associated proteins in yeast, among which is mitochondrial aconitase (Aco1p). We show that this Krebs-cycle enzyme is essential for mtDNA maintenance independent of its catalytic activity. Regulation of ACO1 expression by the HAP and retrograde metabolic signaling pathways directly affects mtDNA maintenance. When constitutively expressed, Aco1p can replace the mtDNA packaging function of the high-mobility-group protein Abf2p. Thus, Aco1p may integrate metabolic signals and mtDNA maintenance.
Chen
Xin Jie
XJ
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Wang
Xiaowen
X
Kaufman
Brett A
BA
Butow
Ronald A
RA
D000483:Alleles; D019943:Amino Acid Substitution; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005947:Glucose / Q000378:metabolism; D035941:Iron Regulatory Protein 1 / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013172:Spores, Fungal / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014170:Transformation, Genetic
C072843:ABF2 protein, S cerevisiae; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D023081:CCAAT-Binding Factor; D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C061437:HAP4 protein, S cerevisiae; C080921:MKS1 protein, S cerevisiae; C079378:RTG1 protein, S cerevisiae; C104438:RTG3 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D035941:Iron Regulatory Protein 1; D005947:Glucose