TOM20-mediated transfer of Bcl2 from ER to MAM and mitochondria upon induction of apoptosis.

Lisenn Lalier, Vincent Mignard, Marie-Pierre Joalland, Didier Lanoé, Pierre-François Cartron, Stéphen Manon, François M Vallette

Cell death & disease 2021 Feb 15

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In this work, we have explored the subcellular localization of Bcl2, a major antiapoptotic protein. In U251 glioma cells, we found that Bcl2 is localized mainly in the ER and is translocated to MAM and mitochondria upon induction of apoptosis; this mitochondrial transfer was not restricted to the demonstrator cell line, even if cell-specific modulations exist. We found that the Bcl2/mitochondria interaction is controlled by TOM20, a protein that belongs to the protein import machinery of the mitochondrial outer membrane. The expression of a small domain of interaction of TOM20 with Bcl2 potentiates its anti-apoptotic properties, which suggests that the Bcl2-TOM20 interaction is proapoptotic. The role of MAM and TOM20 in Bcl2 apoptotic mitochondrial localization and function has been confirmed in a yeast model in which the ER-mitochondria encounter structure (ERMES) complex (required for MAM stability in yeast) has been disrupted. Bcl2-TOM20 interaction is thus an additional player in the control of apoptosis.

Citation

Lisenn Lalier, Vincent Mignard, Marie-Pierre Joalland, Didier Lanoé, Pierre-François Cartron, Stéphen Manon, François M Vallette. TOM20-mediated transfer of Bcl2 from ER to MAM and mitochondria upon induction of apoptosis. Cell death & disease. 2021 Feb 15;12(2):182