Elmore S P, Qian T, Grissom S F, Lemasters J J
Department of Cell and Developmental Biology and Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA.
FASEB J. 2001 Oct;15(12):2286-7. doi: 10.1096/fj.01-0206fje. Epub 2001 Aug 17.
Cells degrade excess and effete organelles by the process of autophagy. Autophagic stimulation of rat hepatocytes by serum deprivation and glucagon (1 M) caused a fivefold increase of spontaneously depolarizing mitochondria to about 1.5% of total mitochondria after 90 min. Cyclosporin A (CsA, 5 M), an immunosuppressant that blocks the mitochondrial permeability transition (MPT), prevented this depolarization. Depolarized mitochondria moved into acidic vacuoles labeled by LysoTracker Red. These autophagosomes also increased several-fold after autophagic stimulation. CsA blocked autophagosomal proliferation, whereas tacrolimus, an immunosuppressant that does not block the MPT, did not. In conclusion, the MPT initiates mitochondrial depolarization after autophagic stimulation and the subsequent sequestration of mitochondria into autophagosomes.
细胞通过自噬过程降解多余和衰老的细胞器。血清剥夺和胰高血糖素（1 μM）对大鼠肝细胞进行自噬刺激后，90分钟内自发去极化的线粒体增加了五倍，达到线粒体总数的约1.5%。环孢素A（CsA，5 μM）是一种阻断线粒体通透性转换（MPT）的免疫抑制剂，可防止这种去极化。去极化的线粒体进入用溶酶体追踪染料标记的酸性液泡中。自噬刺激后，这些自噬体也增加了几倍。CsA阻断自噬体增殖，而不阻断MPT的免疫抑制剂他克莫司则没有这种作用。总之，MPT在自噬刺激后启动线粒体去极化，并随后将线粒体隔离到自噬体中。
