Young J C, Gould J A, Kola I, Iannello R C
Molecular Genetics and Development Laboratory, Monash University, Clayton, Victoria, Australia.
J Exp Zool. 1998;282(1-2):231-8.
Pyruvate dehydrogenase (PDH) is a multiunit enzymatic complex essential for the process of generating cellular energy. One of the most important of its subunits is the E1 alpha subunit. Perturbations in the expression of this subunit lead to reduced or lost function of the PDH complex as a whole, resulting in a loss of ATP production. The consequence of such perturbations can lead to neurological abnormalities, lactic acidosis, and in males, death. Pdha-2 codes for the mouse testis isoform of the E1 alpha subunit and maps to chromosome 19 (chromosome 4 in humans). This is a fortuitous evolutionary development because the somatic isoform of the E1 alpha subunit is linked to the X-chromosome, which is not only inactivated early in spermatogenesis but is represented in only half of the haploid spermatid population. Consequently, activation 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 regulation of Pdha-2 have, until recently, remained poorly understood. In this review, we describe our current understanding of the transcriptional regulation of Pdha-2 and propose potential mechanisms that may play a role in this process.
丙酮酸脱氢酶（PDH）是一种多亚基酶复合物，对细胞能量生成过程至关重要。其最重要的亚基之一是E1α亚基。该亚基表达的扰动会导致整个PDH复合物功能降低或丧失，从而导致ATP生成减少。这种扰动的后果可导致神经异常、乳酸酸中毒，在雄性中还可导致死亡。Pdha - 2编码E1α亚基的小鼠睾丸同工型，定位于19号染色体（人类为4号染色体）。这是一个偶然的进化发展，因为E1α亚基的体细胞同工型与X染色体相连，X染色体不仅在精子发生早期失活，而且仅存在于一半的单倍体精子细胞群体中。因此，睾丸特异性E1α亚基的激活对于精子发生的进展至关重要。尽管其很重要，但直到最近，控制Pdha - 2严格的组织和时间特异性调控的分子机制仍知之甚少。在这篇综述中，我们描述了目前对Pdha - 2转录调控的理解，并提出了可能在这一过程中发挥作用的潜在机制。
