P-32 PROTEIN, A SPLICING FACTOR 2-ASSOCIATED PROTEIN, IS LOCALIZED INMITOCHONDRIAL MATRIX AND IS FUNCTIONALLY IMPORTANT IN MAINTAINING OXIDATIVE-PHOSPHORYLATION

Human p32, originally cloned as a splicing factor 2-associated protein , has been reported to interact with a variety of molecules including human immunodeficiency virus Tat and complement Iq (Clq). p32 protein is supposed to be in the nucleus and on the plasma membrane for the as sociation with human immunodeficiency virus Tat and Clq, respectively. None of the interactions, however, is proven to have a physiological role. To investigate the physiological function of p32, we determined the intracellular localization of p32. The fractionation of cells, flu orescent immunocytochemistry, and electron microscopic immunostaining show that p32 is exclusively localized in the mitochondrial matrix. We cloned a Saccharomyces cerevisiae homologue of human p32 gene, referr ed to yeast p30 gene. The yeast p30 protein is also localized in the m itochondrial matrix. The disruption of the p30 gene caused the growth retardation of yeast cells in a glycerol medium but not in a glucose m edium, i.e. the impairment of the mitochondrial ATP synthesis. The gro wth impairment was restored by the introduction of the human p32 cDNA, indicating that p30 is a functional yeast counterpart of human p32. T aken together, both p32 and p30 reside in mitochondrial matrix and pla y an important role in maintaining mitochondrial oxidative phosphoryla tion.