The increase in mitochondrial association with actin precedes Bax translocation in apoptosis.
Accumulating evidence indicates the potential role of actin cytoskeleton in facilitating the mitochondrial recruitment of various pro-apoptotic proteins from the cytosol to initiate apoptosis. In the present paper, we report the observation of the increase in mitochondrial association of actin in early apoptosis. Using cell fractionation and Western blot analysis, we found that mitochondrial accumulation of beta-actin occurred before the mitochondrial insertion of Bax and release of cytochrome c in apoptosis. The mitochondrial accumulation of beta-actin was observed with various apoptotic stimuli in various cell lines, suggesting that this is a general apoptotic phenomenon in mammalian systems. Using fluorescence microscopy, we have shown that an apoptotic induction triggered the reorganization of the F-actin (filamentous actin) network with an increase in the association with mitochondria, which was observed before mitochondrial fission and nuclear condensation. Perhaps actin could contribute to the initiation of apoptosis by enabling cytosolic pro-apoptotic proteins to be carried to mitochondria by the cytoskeleton-driven trafficking system.
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China.
Ho Lam
HL
Tang
Anh-Huy Phan
AH
Le
Hong Lok
HL
Lung
D000199:Actins / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D019556:COS Cells / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D006367:HeLa Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008928:Mitochondria / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D019311:Staurosporine / Q000494:pharmacology; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D000199:Actins; C494826:BAX protein, human; D016895:Culture Media, Serum-Free; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D019311:Staurosporine