CGC Bibliography Paper 4884

Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria.

Lemieux J, Lakowski B, Webb A, Meng Y, Ubach A, Bussiere F, Barnes T, Hekimi S

Medline:

11560893

Citation:

Genetics 159: 147-157 2001

Type:

ARTICLE

Genes:

gop-1 gop-2 gop-3 gro-1 hap-1 sDf121

Abstract:

We show that the phenotype associated with gro-1(e2400) comprises the whole suite of features that characterize the phenotype of the dl mutants in Caenorhabditis elegans, including deregulated developmental, behavioral, and reproductive rates, as well as increased life span and a maternal effect. We cloned gro-1 and found that it encodes a highly conserved cellular enzyme, isopentenylpyroptiosphate:tRNA transferase (IPT), which modifies a subset of tRNTAs. In yeast, two forms of the enzyme are produced by alternative translation initiation, oric of which is mitochondrial. In the gro-1 transcript there are also two possible initiator ATGs, between which there is a sequence predicted to encode a mitochondrial localization signal. A functional GRO-1::GFP fusion protein is localized diffusely throughout the cytoplasm and nucleus. A GRO-1:GFP initiated from the first methionine is localized exclusively to the mitochondria and rescues the mutant phenotype. In contrast, a protein initiated from the second methionine is localized diffusely throughout the cell and does not rescue the mutant phenotype. As oxygen consumption and ATP concentration have been reported to be unaffected in gro-1 mutants, our observations suggest that GRO-1 acts in mitochondria and regulates global physiology by unknown mechanisms.