YEAST MITOCHONDRIAL NAD-DEPENDENT ISOCITRATE DEHYDROGENASE IS AN RNA-BINDING PROTEIN()

We have previously described the characterisation of an abundant mitoc hondrial protein (p40) that binds specifically to 5'-untranslated lead ers of mitochondrial mRNAs in yeast. p40 consists of two polypeptides with M(r) of 40 and 39 kDa. Limited sequence analysis of p40 identifie s it as the Krebs cycle enzyme NAD+-dependent isocitrate dehydrogenase (Idh). Both enzyme and RNA-binding activities are specifically lost i n cells containing disruptions in either IDH1 or IDH2, the nuclear gen es encoding the two subunits of the enzyme, thus conclusively identify ing p40 as ldh and showing that both activities are dependent on the s imultaneous presence of both subunits. Although we still must ascertai n whether and how either function of ldh is regulated and whether the two functions are compatible or mutually exclusive, this combination o f dehydrogenase activity and RNA-binding in a single protein may be pa rt of a general regulatory circuit linking the need for mitochondrial function to mitochondrial biogenesis.