Department of Structural Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany.
Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15301-6. doi: 10.1073/pnas.1305462110. Epub 2013 Sep 4.
Aging is one of the most fundamental, yet least understood biological processes that affect all forms of eukaryotic life. Mitochondria are intimately involved in aging, but the underlying molecular mechanisms are largely unknown. Electron cryotomography of whole mitochondria from the aging model organism Podospora anserina revealed profound age-dependent changes in membrane architecture. With increasing age, the typical cristae disappear and the inner membrane vesiculates. The ATP synthase dimers that form rows at the cristae tips dissociate into monomers in inner-membrane vesicles, and the membrane curvature at the ATP synthase inverts. Dissociation of the ATP synthase dimer may involve the peptidyl prolyl isomerase cyclophilin D. Finally, the outer membrane ruptures near large contact-site complexes, releasing apoptogens into the cytoplasm. Inner-membrane vesiculation and dissociation of ATP synthase dimers would impair the ability of mitochondria to supply the cell with sufficient ATP to maintain essential cellular functions.
衰老（aging）是影响所有真核生物形式的最基本但也是最不为人知的生物学过程之一。线粒体与衰老密切相关，但潜在的分子机制在很大程度上尚不清楚。来自衰老模式生物米黑毛霉（Podospora anserina）的完整线粒体的电子晶体学断层扫描揭示了膜结构在衰老过程中发生的深刻变化。随着年龄的增长，典型的嵴消失，内膜出现小泡。在嵴尖形成排的 ATP 合酶二聚体解离成内膜小泡中的单体，ATP 合酶处的膜曲率反转。ATP 合酶二聚体的解离可能涉及肽基脯氨酰顺反异构酶 cyclophilin D。最后，外膜在大接触位点复合物附近破裂，将凋亡原释放到细胞质中。内膜小泡化和 ATP 合酶二聚体的解离会损害线粒体为细胞提供足够 ATP 的能力，从而维持基本的细胞功能。
