Arama Eli, Bader Maya, Srivastava Mayank, Bergmann Andreas, Steller Hermann
Strang Laboratory of Cancer Research, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
EMBO J. 2006 Jan 11;25(1):232-43. doi: 10.1038/sj.emboj.7600920. Epub 2005 Dec 15.
Cytochrome C has two apparently separable cellular functions: respiration and caspase activation during apoptosis. While a role of the mitochondria and cytochrome C in the assembly of the apoptosome and caspase activation has been established for mammalian cells, the existence of a comparable function for cytochrome C in invertebrates remains controversial. Drosophila possesses two cytochrome c genes, cyt-c-d and cyt-c-p. We show that only cyt-c-d is required for caspase activation in an apoptosis-like process during spermatid differentiation, whereas cyt-c-p is required for respiration in the soma. However, both cytochrome C proteins can function interchangeably in respiration and caspase activation, and the difference in their genetic requirements can be attributed to differential expression in the soma and testes. Furthermore, orthologues of the apoptosome components, Ark (Apaf-1) and Dronc (caspase-9), are also required for the proper removal of bulk cytoplasm during spermatogenesis. Finally, several mutants that block caspase activation during spermatogenesis were isolated in a genetic screen, including mutants with defects in spermatid mitochondrial organization. These observations establish a role for the mitochondria in caspase activation during spermatogenesis.
细胞色素C具有两种明显可分离的细胞功能：呼吸作用以及细胞凋亡过程中的半胱天冬酶激活。虽然线粒体和细胞色素C在哺乳动物细胞凋亡小体组装和半胱天冬酶激活中的作用已得到证实，但细胞色素C在无脊椎动物中是否具有类似功能仍存在争议。果蝇拥有两个细胞色素c基因，即cyt-c-d和cyt-c-p。我们发现，在精子细胞分化过程中的类凋亡过程中，只有cyt-c-d是半胱天冬酶激活所必需的，而cyt-c-p是体细胞呼吸所必需的。然而，两种细胞色素C蛋白在呼吸作用和半胱天冬酶激活中都可以互换发挥功能，它们在基因需求上的差异可归因于在体细胞和睾丸中的差异表达。此外，凋亡小体成分Ark（Apaf-1）和Dronc（半胱天冬酶-9）的直系同源物在精子发生过程中对大量细胞质的正常清除也是必需的。最后，在遗传筛选中分离出了几个在精子发生过程中阻断半胱天冬酶激活的突变体，包括精子细胞线粒体组织有缺陷的突变体。这些观察结果确立了线粒体在精子发生过程中半胱天冬酶激活中的作用。
