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The mitochondrial permeability transition initiates autophagy in rat hepatocytes
Author(s) -
Elmore Steven P.,
Qian Ting,
Grissom Sherry F.,
Lemasters John J.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0206fje
Subject(s) - autophagy , depolarization , mitochondrion , mitochondrial permeability transition pore , vacuole , microbiology and biotechnology , stimulation , organelle , chemistry , biology , mitophagy , biophysics , biochemistry , programmed cell death , cytoplasm , endocrinology , apoptosis
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.