Disease relevance of CIT1

• The amino terminus of the CIT1 primary translation product extends 39 residues beyond the amino termini of Escherichia coli and porcine citrate synthases [1].

High impact information on CIT1

• Here we report on the characterization of 15 point mutations and a complete deletion of the cit1 gene, which encodes mCS in the filamentous fungus Podospora anserina [2].
• However, they display an unexpected developmental phenotype: in homozygous crosses, cit1 mutations impair meiosis progression beyond the diffuse stage, a key stage of meiotic prophase [2].
• Most of the aneuploid regions were the result of translocations, including three instances of a shared breakpoint on chromosome 14 immediately adjacent to CIT1, which encodes the citrate synthase that performs a key regulated step in the tricarboxylic acid cycle [3].
• We show that the cis-acting sequence controlling RTG-dependent expression of CIT1 includes an R box element, GTCAC, located 70 bp upstream of the Hap2,3,4,5p binding site in the CIT1 upstream activation sequence [4].
• The peroxisomal form, encoded by CIT2, terminates in SKL, while the mitochondrial form, encoded by CIT1, begins with an amino-terminal mitochondrial signal sequence and ends in SKN [5].

Biological context of CIT1

• Second, the poor growth phenotype could be suppressed by the presence of mutations in CIT1 and other genes encoding oxidative functions [6].
• Spontaneous suppressor mutants that restore fast growth on glycerol medium to strains harboring two idh2 alleles were isolated, and a large percentage of the suppressor mutations have been identified within the CIT1 gene and at several other loci [6].
• Mutations in the IDH2 gene encoding the catalytic subunit of the yeast NAD+-dependent isocitrate dehydrogenase can be suppressed by mutations in the CIT1 gene encoding citrate synthase and other genes of oxidative metabolism [6].
• To analyze the function of the N-terminal region of Cit2p in protein trafficking, we constructed the N-terminal domain-swapped versions of Cit1p and Cit2p [7].
• The DNA sequence of CIT2 presented provides a possible explanation for why the CIT2 product, unlike the CIT1 product, fails to be imported into mitochondria [1].

Anatomical context of CIT1

• Saccharomyces cerevisiae has three distinct citrate synthases, two located in mitochondria (mature Cit1p and Cit3p) and one in peroxisomes (mature Cit2p) [7].
• Cit2p was able, when mislocalized in mitochondria, to restore a wild-type phenotype in a strain lacking Cit1p [8].

Associations of CIT1 with chemical compounds

• Genes CIT1 and CIT2 from Saccharomyces cerevisiae encode mitochondrial and peroxisomal citrate synthases involved in the Krebs tricarboxylic acid (TCA) cycle and glyoxylate pathway, respectively [8].
• Both fusions, Cit1::Cit2 and Cit2::Cit1, complemented the glutamate auxotrophy caused by the double-disruption of the CIT1 and CIT2 genes [7].
• CIT2 expression was also increased in [rho+] cells by inhibition of respiration with antimycin A or in [rho+] cells containing a disruption of the CIT1 gene [9].
• Transcription of CIT1 is subject to glucose repression [10].
• Mutant glu3 unlike aconitaseless glutamic acid auxotroph glu 1, failed to accumulate 14C-citric acid in vivo from 1-14C-sodium acetate or U-14C-glutamic acid [11].

Regulatory relationships of CIT1

• The CIT3 gene seems to be regulated in the same way as CIT1, which encodes the mitochondrial isoform of citrate synthase [12].

Other interactions of CIT1

• These data provide the first direct in vivo evidence of interaction between two sequential tricarboxylic acid cycle enzymes, Cit1p and Mdh1p, and indicate that the characterization of assembly mutations by the reversible transdominant inhibition method may be a powerful way to study multienzyme complexes in their physiological context [13].
• On chromosome XIV, the duplicated fragment included the centromere, four genes (FUN34, CIT1 and two tDNAs), one open reading frame (DOM34) and a truncated delta element [14].
• The ensuing evolution of the duplicated regions retained strict sequence identity for the two tDNAs pairs, but was partially divergent for CIT1 and FUN34, and generated a probable pseudogenic equivalent of DOM34 on chromosome III [14].

References