Genome-wide responses to mitochondrial dysfunction.
Mitochondrial dysfunction can lead to diverse cellular and organismal responses. We used DNA microarrays to characterize the transcriptional responses to different mitochondrial perturbations in Saccharomyces cerevisiae. We examined respiratory-deficient petite cells and respiratory-competent wild-type cells treated with the inhibitors of oxidative phosphorylation antimycin, carbonyl cyanide m-chlorophenylhydrazone, or oligomycin. We show that respiratory deficiency, but not inhibition of mitochondrial ATP synthesis per se, induces a suite of genes associated with both peroxisomal activities and metabolite-restoration (anaplerotic) pathways that would mitigate the loss of a complete tricarboxylic acid cycle. The array data suggested, and direct microscopic observation of cells expressing a derivative of green fluorescent protein with a peroxisomal matrix-targeting signal confirmed, that respiratory deficiency dramatically induces peroxisome biogenesis. Transcript profiling of cells harboring null alleles of RTG1, RTG2, or RTG3, genes known to control signaling from mitochondria to the nucleus, suggests that there are multiple pathways of cross-talk between these organelles in yeast.
Epstein
C B
CB
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.
Waddle
J A
JA
Hale
W
W
Davé
V
V
Thornton
J
J
Macatee
T L
TL
Garner
H R
HR
Butow
R A
RA
D000968:Antimycin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002952:Citric Acid Cycle; D004268:DNA-Binding Proteins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D016681:Genome, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D020675:Peroxisomes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011422:Propionates / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009840:Oligomycins; D011422:Propionates; C079378:RTG1 protein, S cerevisiae; C079379:RTG2 protein, S cerevisiae; C104438:RTG3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C032456:antimycin; D000968:Antimycin A; C029658:propionic acid