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The mitochondrial permeability transition initiates autophagy in rat hepatocytes
Abstract
Cells degrade excess and effete organelles by the process of autophagy. Autophagic stimulation of rat hepatocytes by serum deprivation and glucagon (1 µM) caused a fivefold increase of spontaneously depolarizing mitochondria to about 1.5% of total mitochondria after 90 min. Cyclosporin A (CsA, 5 µM), 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.
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Citations
Cited by
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Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124
Metadata
- Authors
- Elmore, S. P., Qian, T., Grissom, S. F., & Lemasters, J. J.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2001-08-17
- Volume
- 15
- Issue
- 12
- Pages
- 1-17
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2144687501
- Cited by
- 606
- References
- 0
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- closed
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- Elmore, S. P., Qian, T., Grissom, S. F., & Lemasters, J. J. (2001). The mitochondrial permeability transition initiates autophagy in rat hepatocytes. The FASEB Journal. https://doi.org/10.1096/fj.01-0206fje
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