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

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 Cae norhabditis elegans, including deregulated developmental, behavioral, and r eproductive 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 tr anslation initiation, oric of which is mitochondrial. In the gro-1 transcri pt there are also two possible initiator ATGs, between which there is a seq uence 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 e xclusively to the mitochondria and rescues the mutant phenotype. In contras t, a protein initiated from the second methionine is localized diffusely th roughout the cell and does not rescue the mutant phenotype. As oxygen consu mption and ATP concentration have been reported to be unaffected in gro-1 m utants, our observations suggest that GRO-1 acts in mitochondria and regula tes global physiology by unknown mechanisms.