The two Drosophila cytochrome C proteins can function in both respiration and caspase activation
The two Drosophila cytochrome C proteins can function in both respiration and caspase activation
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DOI：
10.1038/sj.emboj.7600920
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发表时间：
2006-01-11
期刊：
影响因子：
11.4
通讯作者：
Steller, H
中科院分区：
文献类型：
--
作者：
Arama, E;Bader, M;Steller, H
细胞色素 C 具有两种明显可分离的细胞功能：细胞凋亡过程中的呼吸和 caspase 激活。虽然哺乳动物细胞中线粒体和细胞色素 C 在凋亡体组装和半胱天冬酶激活中的作用已经确定，但无脊椎动物中细胞色素 C 是否存在类似功能仍存在争议。果蝇拥有两个细胞色素c基因，cyt-c-d和cyt-c-p。我们发现，在精子细胞分化过程中的凋亡样过程中，仅 cyt-c-d 是 caspase 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 蛋白在呼吸和半胱天冬酶激活中可以互换，并且它们遗传需求的差异可归因于体细胞和睾丸中的差异表达。此外，凋亡体成分 Ark (Apaf-1) 和 Dronc (caspase-9) 的直向同源物也是在精子发生过程中正确去除大量细胞质所必需的。最后，在遗传筛选中分离出了几种在精子发生过程中阻断 caspase 激活的突变体，其中包括精子细胞线粒体组织有缺陷的突变体。这些观察结果确定了线粒体在精子发生过程中半胱天冬酶激活中的作用。
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.