REVIEW - PDHA-2, PAST AND PRESENT

Pyruvate dehydrogenase (PDH) is a multiunit enzymatic complex essentia l for the process of generating cellular energy. One of the most impor tant of its subunits is the E1 alpha subunit. Perturbations in the exp ression of this subunit lead to reduced or lost function of the PDH co mplex as a whole, resulting in a loss of ATP production. The consequen ce of such perturbations can lead to neurological abnormalities, lacti c acidosis, and in males, death. Pdha-2 codes for the mouse testis iso form of the E1 alpha subunit and maps to chromosome 19 (chromosome 4 i n humans). This is a fortuitous evolutionary development because the s omatic isoform of the E1 alpha subunit is linked to the X-chromosome, which is not only inactivated early in spermatogenesis but is represen ted in only half of the haploid spermatid population. Consequently, ac tivation of the testis-specific E1 alpha subunit is essential for the progression of spermatogenesis. Despite its importance, the molecular mechanisms governing the tight tissue- and temporal-specific regulatio n of Pdha-2 have, until recently, remained poorly understood. In this review, we describe our current understanding of the transcriptional r egulation of Pdha-2 and propose potential mechanisms that may play a r ole in this process. J. Exp. Zool. 282:231-238, 1998. (C) 1998 Wiley-L iss, Inc.